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Ramos B, Vadlamudi NK, Han C, Sadarangani M. Future immunisation strategies to prevent Streptococcus pneumoniae infections in children and adults. THE LANCET. INFECTIOUS DISEASES 2025; 25:e330-e344. [PMID: 40112854 DOI: 10.1016/s1473-3099(24)00740-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/28/2024] [Accepted: 10/29/2024] [Indexed: 03/22/2025]
Abstract
Streptococcus pneumoniae is a major respiratory pathogen, causing 1·2 million deaths and 197 million pneumonia episodes globally in 2016. The spread of S pneumoniae to sterile sites, such as the blood and brain, leads to invasive pneumococcal disease. The best approach available for prevention of invasive pneumococcal disease in children and, more recently, adults is the use of pneumococcal conjugate vaccines (PCVs). PCVs are also highly effective at preventing colonisation and, thus, transmission, offering indirect protection to non-target immunisation groups such as adults-a characteristic that has been crucial in their success. However, PCVs only include and protect up to 20 of the 100 serotypes that can cause disease. The rise in adult cases of invasive pneumococcal disease from serotypes included in PCVs suggests indirect protection might be limited. Additionally, non-vaccine serotypes and some vaccine types that persist, some linked to antibiotic resistance, continue to cause disease. Future vaccine strategies include increasing the number of serotypes covered in PCVs for use in children and adults, broader vaccine use in adults, the development of adult-specific conjugate vaccines containing serotypes different from those covered in PCVs used in children, and protein vaccines, all of which will be explored in this Review. These strategies are expected to help mitigate the global burden of invasive pneumococcal disease in future years.
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Affiliation(s)
- Bernice Ramos
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada; Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Nirma Khatri Vadlamudi
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Crystal Han
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Manish Sadarangani
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
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Skoczyńska A, Gołębiewska A, Wróbel-Pawelczyk I, Ronkiewicz P, Kiedrowska M, Błaszczyk K, Czerwiński M, Waśko I, Sadkowska-Todys M, Kuch A, Hryniewicz W. The direct impact of mandatory PCV10 vaccination on invasive pneumococcal disease in Polish children. Vaccine 2025; 54:126999. [PMID: 40081231 DOI: 10.1016/j.vaccine.2025.126999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 03/06/2025] [Accepted: 03/06/2025] [Indexed: 03/15/2025]
Abstract
BACKGROUND The introduction of pneumococcal conjugate vaccines (PCVs) into National Immunization Programs (NIP) has led to a significant decrease in pneumococcal infections. This study aimed to evaluate the direct impact of the introduction of PCV10 into the NIP in 2017 on the serotype distribution and antimicrobial susceptibility of pneumococci causing invasive pneumococcal disease (IPD) in Polish children. METHODS The study encompassed all pneumococcal strains responsible for IPD in Polish children under five years of age submitted to the reference centre between July 2013 and June 2023. Four analysis periods were defined: pre-PCV10 (July 2013-June 2016), early post-PCV10 (July 2017-June 2020), COVID-19 pandemic (July 2020-June 2021), and late post-PCV10 (July 2021-June 2023). Routine techniques were utilized for identification, serotyping, and antimicrobial susceptibility testing. RESULTS Following the introduction of PCV10, a significant decline in the proportion of IPD cases caused by PCV10 serotypes in children under five years of age was observed, decreasing from 52.1 % to 8.1 %. Also significant was a decrease of PCV10 serotypes among resistant pneumococci, including MDR isolates which dropped from 65.4 % to 9.8 %. In the late post-PCV10 period, isolates of serotype 19A (37.6 %) and serotype 3 (17.9 %) were the most prevalent. In the late post-PCV10 period, 19A pneumococci accounted for 77.0 % of all MDR cases. CONCLUSIONS The introduction of PCV10 into the Polish NIP significantly reduced infections caused by PCV10 serotypes, including infections associated with resistant pneumococci. Concurrently, we noted an increase in the prevalence of non-PCV10 serotypes, notably serotype 19 A, which presently constitutes one-third of the total infections. The results of our study support the need to introduce a vaccine containing 19A polysaccharides into the Polish NIP and emphasizes the importance of continuous IPD surveillance.
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Affiliation(s)
- Anna Skoczyńska
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
| | - Agnieszka Gołębiewska
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
| | - Izabela Wróbel-Pawelczyk
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
| | - Patrycja Ronkiewicz
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
| | - Marlena Kiedrowska
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
| | - Kinga Błaszczyk
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
| | - Michał Czerwiński
- National Institute of Public Health NIH-National Research Institute (NIPH NIH-NRI), Warsaw, Poland.
| | - Izabela Waśko
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
| | | | - Alicja Kuch
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
| | - Waleria Hryniewicz
- National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Warsaw, Poland.
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Gates CJ, Brazel EB, Kennedy EV, Brown JS, Ercoli G, Davies J, Hirst TR, Paton JC, Alsharifi M. A gamma-irradiated pneumococcal vaccine elicits superior immunogenicity in comparison to heat or chemically inactivated whole-cell vaccines. Vaccine 2025; 54:126982. [PMID: 40048932 DOI: 10.1016/j.vaccine.2025.126982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 11/10/2024] [Accepted: 02/28/2025] [Indexed: 05/13/2025]
Abstract
Streptococcus pneumoniae is one of the world's foremost bacterial pathogens, with extensive serotype diversity that impacted the efficacy of current vaccines. Our group have previously reported the generation of a whole cell serotype-independent gamma-irradiated pneumococcal vaccine (Gamma-PN). The present study sought to compare the effect of gamma-irradiation, heat, ethanol, or formalin inactivation on the antigenic structure and immunogenicity of whole-cell pneumococcal vaccines. Our data demonstrate that Gamma-PN exhibited comparable cellular morphology to live bacteria, in contrast to damage and aggregation observed for other approaches. Vaccination of mice with Gamma-PN or heat-inactivated PN (Heat-PN) induced high levels of pneumococcal-specific IgG, but with significantly different profiles of IgG subclasses. In addition, while immune sera from Heat-PN vaccinated mice had strong PspA-specific responses, sera from Gamma-PN vaccinated animals showed enhanced recognition of a wider array of pneumococcal proteins. Overall, in contrast to other methods of inactivation, the gamma-irradiated pneumococcal vaccine retained cellular structure and elicited immunity against a broad array of pneumococcal proteins, positioning this vaccine well to stimulate robust immunity to pneumococcal disease.
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Affiliation(s)
- Chloe J Gates
- Research Centre for Infectious Diseases and Department of Molecular and Biomedical Sciences, School of Biological Sciences, The University of Adelaide, SA, Australia
| | - Erin B Brazel
- Research Centre for Infectious Diseases and Department of Molecular and Biomedical Sciences, School of Biological Sciences, The University of Adelaide, SA, Australia; GPN Vaccines Ltd, Yarralumla, ACT, Australia
| | | | - Jeremy S Brown
- UCL Respiratory, University College London, London, United Kingdom
| | - Giuseppe Ercoli
- UCL Respiratory, University College London, London, United Kingdom
| | - Justin Davies
- Irradiations Group, Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, NSW, Australia
| | | | - James C Paton
- Research Centre for Infectious Diseases and Department of Molecular and Biomedical Sciences, School of Biological Sciences, The University of Adelaide, SA, Australia; GPN Vaccines Ltd, Yarralumla, ACT, Australia
| | - Mohammed Alsharifi
- Research Centre for Infectious Diseases and Department of Molecular and Biomedical Sciences, School of Biological Sciences, The University of Adelaide, SA, Australia; GPN Vaccines Ltd, Yarralumla, ACT, Australia.
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Mrabt F, Guedes S. Systematic review on serotypes distribution of pneumococcal pneumonia in adults and the elderly. BMC Public Health 2025; 25:1194. [PMID: 40158111 PMCID: PMC11954302 DOI: 10.1186/s12889-025-22164-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 03/02/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND Pneumococcal pneumonia is a major cause of morbidity and mortality among adults, especially those over 65 years of age. Understanding pneumococcal serotype-specific epidemiology in adults and elderly is necessary to inform vaccination policies and to guide the inclusion of serotypes in pneumococcal vaccines. This study aimed to identify the serotypes causing pneumonia in the elderly. METHODS A systematic review search was performed using the PubMed database from 1984 to 2020. The search was limited to articles written in English. Studies assessing pneumococcal pneumonia in adults were included. Meta-analysis, other systematic literature reviews and case-reports were excluded. Studies published after the introduction of vaccines (PPSV23 and PCVs) were included. RESULTS Forty studies were included. The most common serotype identified in the majority of the articles in adults was the serotype 3 followed by serotypes 19A and 11A. Those serotypes are included in current vaccines. Emergence of non-vaccine serotypes was also observed. CONCLUSION Pneumococcal pneumonia remains a high burden in the elderly despite the existence of vaccines for many years. In 2019, nearly 1.4 million deaths were attributable to pneumococcal pneumonia (50% of whom were over 70 years old) and was the leading cause of deaths from infectious disease worldwide. The study highlights the importance of constant monitoring serotypes emerging in this population to better target vaccination strategies.
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Ganaie FA, Beall BW, Yu J, van der Linden M, McGee L, Satzke C, Manna S, Lo SW, Bentley SD, Ravenscroft N, Nahm MH. Update on the evolving landscape of pneumococcal capsule types: new discoveries and way forward. Clin Microbiol Rev 2025; 38:e0017524. [PMID: 39878373 PMCID: PMC11905375 DOI: 10.1128/cmr.00175-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025] Open
Abstract
SUMMARYStreptococcus pneumoniae (the "pneumococcus") is a significant human pathogen. The key determinant of pneumococcal fitness and virulence is its ability to produce a protective polysaccharide (PS) capsule, and anti-capsule antibodies mediate serotype-specific opsonophagocytic killing of bacteria. Notably, immunization with pneumococcal conjugate vaccines (PCVs) has effectively reduced the burden of disease caused by serotypes included in vaccines but has also spurred a relative upsurge in the prevalence of non-vaccine serotypes. Recent advancements in serotyping and bioinformatics surveillance tools coupled with high-resolution analytical techniques have enabled the discovery of numerous new capsule types, thereby providing a fresh perspective on the dynamic pneumococcal landscape. This review offers insights into the current pneumococcal seroepidemiology highlighting important serotype shifts in different global regions in the PCV era. It also comprehensively summarizes newly discovered serotypes from 2007 to 2024, alongside updates on revised chemical structures and the de-novo determinations of structures for previously known serotypes. Furthermore, we spotlight emerging evidence on non-pneumococcal Mitis-group strains that express capsular PS that are serologically and biochemically related to the pneumococcal capsule types. We further discuss the implications of these recent findings on capsule nomenclature, pneumococcal carriage detection, and future PCV design. The review maps out the current status and also outlines the course for future research and vaccine strategies, ensuring a continued effective response to the evolving pneumococcal challenge.
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Affiliation(s)
- Feroze A. Ganaie
- Department of Medicine, Division of Pulmonary/Allergy/Critical Care, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Bernard W. Beall
- Eagle Global Scientific, LLC, Contractor to Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Jigui Yu
- Department of Medicine, Division of Pulmonary/Allergy/Critical Care, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Mark van der Linden
- Reference Laboratory for Streptococci, Department of Medical Microbiology, University Hospital RWTH Aachen, Aachen, Germany
| | - Lesley McGee
- Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Catherine Satzke
- Infection, Immunity and Global Health, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia
- Department of Pediatrics, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia
| | - Sam Manna
- Infection, Immunity and Global Health, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia
| | - Stephanie W. Lo
- Parasites and Microbes, Wellcome Sanger Institute, Cambridge, United Kingdom
- Milner Center for Evolution, Department of Life Sciences, University of Bath, Bath, United Kingdom
| | - Stephen D. Bentley
- Parasites and Microbes, Wellcome Sanger Institute, Cambridge, United Kingdom
| | - Neil Ravenscroft
- Department of Chemistry, University of Cape Town, Rondebosch, South Africa
| | - Moon H. Nahm
- Department of Medicine, Division of Pulmonary/Allergy/Critical Care, The University of Alabama at Birmingham, Birmingham, Alabama, USA
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Negash AA, Ferreira A, Asrat D, Aseffa A, Cools P, Van Simaey L, Vaneechoutte M, Bentley SD, Lo SW. Genomic characterization of Streptococcus pneumoniae isolates obtained from carriage and disease among paediatric patients in Addis Ababa, Ethiopia. Microb Genom 2025; 11:001376. [PMID: 40100271 PMCID: PMC11986848 DOI: 10.1099/mgen.0.001376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 02/03/2025] [Indexed: 03/20/2025] Open
Abstract
Background and aims. Despite the introduction of pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae still remains an important cause of morbidity and mortality, especially among children under 5 years in sub-Saharan Africa. We sought to determine the distribution of serotypes, lineages and antimicrobial resistance of S. pneumoniae from carriage and disease among children presenting to health facilities, 5-6 years after the introduction of PCV10 in Ethiopia.Methods. Whole-genome sequencing (WGS) was performed on 103 S. pneumoniae (86 from nasopharyngeal swabs, 4 from blood and 13 from middle ear discharge) isolated from children aged <15 years at 3 healthcare facilities in Addis Ababa, Ethiopia, from September 2016 to August 2017. Using the WGS data, serotypes were predicted, isolates were assigned to clonal complexes, global pneumococcal sequence clusters (GPSCs) were inferred and screening for alleles and mutations that confer resistance to antibiotics was performed using multiple bioinformatic pipelines.Results. The 103 S. pneumoniae isolates were assigned to 38 serotypes (including nontypeable) and 46 different GPSCs. The most common serotype was serotype 19A. Common GPSCs were GPSC1 [14.6% (15/103), sequence type (ST) 320, serotype 19A], GPSC268 [8.7% (9/103), ST 6882 and novel STs; serotypes 16F, 11A and 35A] and GPSC10 [8.7% (9/103), STs 2013, 230 and 8804; serotype 19A]. The four invasive isolates were serotype 19A (n=2) and serotype 33C (n=2). Resistance to penicillin (>0.06 µg ml-1, CLSI meningitis cutoff) was predicted in 57% (59/103) of the isolates, and 43% (25/58) penicillin-binding protein allele combinations were predicted to be associated with penicillin resistance. Resistance mutations in folA (I100L) and/or folP (indel between fifty-sixth and sixty-seventh aa) were identified among 66% (68/103) of the isolates, whilst tetracycline (tetM) and macrolide (ermB and mefA) resistance genes were found in 46.6% (48/103), 20.4% (21/103) and 20.4% (21/103) of the isolates, respectively. Multidrug resistance (MDR) (≥3 antibiotic classes) was observed in 31.1% (32/103) of the isolates. GPSC1 and GPSC10 accounted for 46.8% (15/32) and 18.7% (6/32) of the overall MDR.Conclusion. Five to 6 years after the introduction of PCV10 in Ethiopia, the S. pneumoniae obtained from carriage and disease among paediatric patients showed diverse serotype and pneumococcal lineages. The most common serotype identified was 19A, expressed by the MDR lineages GPSC1 and GPSC10, which is not covered by PCV10 but is included in PCV13. Continued assessment of the impact of PCV on the population structure of S. pneumoniae in Ethiopia is warranted during and after PCV13 introduction.
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Affiliation(s)
- Abel Abera Negash
- Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
- Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK
- Department of Microbiology, Immunology and Parasitology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Ana Ferreira
- Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK
| | - Daniel Asrat
- Department of Microbiology, Immunology and Parasitology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Abraham Aseffa
- Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
| | - Piet Cools
- Laboratory Bacteriology Research, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Leen Van Simaey
- Laboratory Bacteriology Research, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Mario Vaneechoutte
- Laboratory Bacteriology Research, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | | | - Stephanie W. Lo
- Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK
- Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, UK
- The Great Ormond Street Institute of Child Health, University College London, London, UK
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Yu J, Ravenscroft N, Davey P, Liyanage R, Lorenz O, Kuttel MM, Lo SW, Ganaie FA, Nahm MH. New pneumococcal serotype 20C is a WciG O-acetyltransferase deficient variant of canonical serotype 20B. Microbiol Spectr 2025; 13:e0244324. [PMID: 39612217 PMCID: PMC11705870 DOI: 10.1128/spectrum.02443-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 11/12/2024] [Indexed: 11/30/2024] Open
Abstract
The polysaccharide (PS) capsule of Streptococcus pneumoniae (pneumococcus) is the immunodominant surface structure that shields the bacteria from the host immune system. Since the capsule is the primary target of currently available pneumococcal vaccines, anti-capsular antibodies are highly protective but serotype-specific. Pneumococci may evade host or vaccine-induced immunity as a result of variation in capsule structure mediated via multiple mechanisms, such as the loss or gain of O-acetylation. Previous biochemical studies of serogroup 20 isolates have identified two subtypes-20A and 20B, whose capsule PS differs in the WhaF-mediated glucose side chain. Herein, we characterize a newly discovered capsule type, 20C, that differs from serotype 20B via the inactivation of capsule O-acetyltransferase gene, wciG. Structural analysis demonstrated that 20C and 20B share an identical repeat unit [→3)-α-D-GlcpNAc-[β-D-Galf-(1→4)][α-D-Glcp-(1→6)]-(1→P→6)-α-D-Glcp-(1→6)- β-D-Glcp-(1→3)-β-D-Galf 5,6Ac2-(1→3)-β-D-Glcp-(1→], except for the absence of WciG-mediated O-acetyl group at terminal galactofuranose (β-D-Galf). We confirmed that deletion of the wciG gene in a 20B strain resulted in the expression of the 20C capsule. Serotype 20C is serologically indistinguishable from the canonical 20A and 20B using conventional serotyping antibodies, but serogroup 20 subtypes can be distinguished by sequencing of cps genes-whaF, wciG, and wcjE. While genetic screening suggests 20C to be globally less prevalent, a new variant was identified which appears to have both wciG and whaF genes inactive, potentially indicating it to be a new serotype. Consequently, genome-based serotyping/bioinformatic tools must scrutinize all cps genes for mutations that might inactivate/modify cps-encoded enzymes, ensuring effective tracking of emerging capsule variants in response to ongoing vaccination efforts. IMPORTANCE Streptococcus pneumoniae (pneumococcus) is a significant human pathogen known for producing a wide array of antigenically and structurally diverse capsule types, a fact that poses a serious challenge to the effectiveness of vaccines targeting pneumococcal capsule polysaccharide (PS). Herein, we provide a comprehensive analysis-genetic, antigenic, and biochemical of a newly identified capsule type, 20C, which differs from the canonical serotype 20B due to the inactivation of the capsule O-acetyltransferase gene, wciG. Our findings highlight how pneumococci can alter their capsule PS structure and immunological characteristics through minor genetic modifications. Since the appearance of new capsule types can directly affect pneumococcal conjugate vaccine (PCV) implementation, a deeper understanding of capsule PS at the genetic, immunological, and biochemical levels is critical for the development of future diagnostic tools and vaccines.
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Affiliation(s)
- Jigui Yu
- Department of Medicine, Division of Pulmonary/Allergy/Critical Care, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Neil Ravenscroft
- Department of Chemistry, University of Cape Town, Rondebosch, South Africa
| | | | | | - Oliver Lorenz
- Parasites and Microbes, Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom
| | - Michelle M. Kuttel
- Department of Computer Science, University of Cape Town, Rondebosch, South Africa
| | - Stephanie W. Lo
- Parasites and Microbes, Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom
- Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, United Kingdom
| | - Feroze A. Ganaie
- Department of Medicine, Division of Pulmonary/Allergy/Critical Care, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Moon H. Nahm
- Department of Medicine, Division of Pulmonary/Allergy/Critical Care, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Pizzutti K, Comerlato J, de Oliveira DV, Robaina A, Mott MP, Vieira PUP, Fetzner T, da Cunha GR, de Barros MP, Verardo J, Bruscato NM, Santana JCB, Corte RRD, Moriguchi EH, Cantarelli VV, Dias CAG. Nasopharyngeal carriage of Streptococcus pneumoniae among Brazilian children: Interplay with viral co-infection. PLoS One 2025; 20:e0316444. [PMID: 39746082 PMCID: PMC11694996 DOI: 10.1371/journal.pone.0316444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 12/11/2024] [Indexed: 01/04/2025] Open
Abstract
Nasopharyngeal transmission of Streptococcus pneumoniae is a prerequisite for the development of pneumococcal diseases. Previous studies have reported a relationship between respiratory viruses and S. pneumoniae infections. However, there are few studies on this issue among healthy children. This study aimed to examine the relationships between these agents in healthy children from Southern Brazil. This cohort study included 229 nasopharyngeal samples collected from children aged 18-59 months at baseline. S. pneumoniae was detected using bacterial culture, whereas respiratory viruses were identified using quantitative polymerase chain reaction. A questionnaire was used at the time of sample collection and medical records were reviewed 14 days after participant inclusion. The prevalence of pneumococcal carriage was 63.7% (146/229), while respiratory viruses were detected in 49.3% (113/229) of the children. Respiratory viruses were more frequently found among pneumococcal carriers than among non-carriers (54.4% vs. 39.7%, p = 0.033). Additionally, rhinovirus (hRV) was more frequent among the pneumococcal carriers (39% vs. 21.7%, p = 0.012), and the presence of human bocavirus (hBOV) alone was associated with the absence of pneumococcal carriage (2.7% vs. 10.8%, p = 0.016). No differences were found in the frequency of pneumococcal carriage, respiratory virus detection, or the co-occurrence of clinical symptoms and diagnosis in the participants 14 days after specimen collection. Our findings revealed a positive relationship between pneumococcal carriage and respiratory virus detection, particularly for hRV. However, we did not observe a relationship between nasopharyngeal respiratory viruses and pneumococci detection during medical appointments, respiratory symptoms, or diseases. This study was one of the first investigations in Latin America to explore the relationship between respiratory viruses and pneumococcal carriage in a healthy children.
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Affiliation(s)
- Kauana Pizzutti
- Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
| | - Juliana Comerlato
- Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
- Hospital Moinhos de Vento, Porto Alegre, RS, Brazil
| | | | - Amanda Robaina
- Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
| | | | | | - Tiago Fetzner
- Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
| | | | | | - Jaqueline Verardo
- Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil
| | - Neide Maria Bruscato
- Moriguchi Institute, Veranópolis, RS, Brazil
- Community Hospital São Peregrino Lazziozi, Veranópolis, RS, Brazil
| | | | | | - Emilio Hideyuki Moriguchi
- Moriguchi Institute, Veranópolis, RS, Brazil
- Hospital of Health Clinic of Porto Alegre, Porto Alegre, RS, Brazil
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Rodriguez-Ruiz JP, Xavier BB, Stöhr W, van Heirstraeten L, Lammens C, Finn A, Goossens H, Bielicki JA, Sharland M, Malhotra-Kumar S. High-resolution genomics identifies pneumococcal diversity and persistence of vaccine types in children with community-acquired pneumonia in the UK and Ireland. BMC Microbiol 2024; 24:146. [PMID: 38678217 PMCID: PMC11055344 DOI: 10.1186/s12866-024-03300-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 04/11/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Streptococcus pneumoniae is a global cause of community-acquired pneumonia (CAP) and invasive disease in children. The CAP-IT trial (grant No. 13/88/11; https://www.capitstudy.org.uk/ ) collected nasopharyngeal swabs from children discharged from hospitals with clinically diagnosed CAP, and found no differences in pneumococci susceptibility between higher and lower antibiotic doses and shorter and longer durations of oral amoxicillin treatment. Here, we studied in-depth the genomic epidemiology of pneumococcal (vaccine) serotypes and their antibiotic resistance profiles. METHODS Three-hundred and ninety pneumococci cultured from 1132 nasopharyngeal swabs from 718 children were whole-genome sequenced (Illumina) and tested for susceptibility to penicillin and amoxicillin. Genome heterogeneity analysis was performed using long-read sequenced isolates (PacBio, n = 10) and publicly available sequences. RESULTS Among 390 unique pneumococcal isolates, serotypes 15B/C, 11 A, 15 A and 23B1 were most prevalent (n = 145, 37.2%). PCV13 serotypes 3, 19A, and 19F were also identified (n = 25, 6.4%). STs associated with 19A and 19F demonstrated high genome variability, in contrast to serotype 3 (n = 13, 3.3%) that remained highly stable over a 20-year period. Non-susceptibility to penicillin (n = 61, 15.6%) and amoxicillin (n = 10, 2.6%) was low among the pneumococci analysed here and was independent of treatment dosage and duration. However, all 23B1 isolates (n = 27, 6.9%) were penicillin non-susceptible. This serotype was also identified in ST177, which is historically associated with the PCV13 serotype 19F and penicillin susceptibility, indicating a potential capsule-switch event. CONCLUSIONS Our data suggest that amoxicillin use does not drive pneumococcal serotype prevalence among children in the UK, and prompts consideration of PCVs with additional serotype coverage that are likely to further decrease CAP in this target population. Genotype 23B1 represents the convergence of a non-vaccine genotype with penicillin non-susceptibility and might provide a persistence strategy for ST types historically associated with vaccine serotypes. This highlights the need for continued genomic surveillance.
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Affiliation(s)
- Juan Pablo Rodriguez-Ruiz
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Universiteit Antwerpen, Antwerp, Belgium
| | - Basil Britto Xavier
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Universiteit Antwerpen, Antwerp, Belgium
| | - Wolfgang Stöhr
- MRC Clinical Trials Unit, University College London, London, UK
| | - Liesbet van Heirstraeten
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Universiteit Antwerpen, Antwerp, Belgium
| | - Christine Lammens
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Universiteit Antwerpen, Antwerp, Belgium
| | | | - Herman Goossens
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Universiteit Antwerpen, Antwerp, Belgium
| | - Julia Anna Bielicki
- Paediatric Infectious Diseases Research Group, St George's University of London, London, UK
| | - Michael Sharland
- Paediatric Infectious Diseases Research Group, St George's University of London, London, UK
| | - Surbhi Malhotra-Kumar
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Universiteit Antwerpen, Antwerp, Belgium.
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10
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Rodrigues TC, Figueiredo DB, Gonçalves VM, Kaneko K, Saleem IY, Miyaji EN. Liposome-based dry powder vaccine immunization targeting the lungs induces broad protection against pneumococcus. J Control Release 2024; 368:184-198. [PMID: 38395155 DOI: 10.1016/j.jconrel.2024.02.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 02/05/2024] [Accepted: 02/20/2024] [Indexed: 02/25/2024]
Abstract
Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4+ resident memory T cells were detected in the lungs of the immunized animals that survived the challenge.
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Affiliation(s)
- T C Rodrigues
- Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil; Programa de Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, Brazil
| | - D B Figueiredo
- Programa de Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, Brazil; Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil
| | - V M Gonçalves
- Programa de Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, Brazil; Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil
| | - K Kaneko
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, Merseyside, United Kingdom
| | - I Y Saleem
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, Merseyside, United Kingdom.
| | - E N Miyaji
- Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil; Programa de Pós-Graduação Interunidades em Biotecnologia, Universidade de São Paulo, São Paulo, Brazil.
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11
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Rafiqullah IM, Varghese R, Hellmann KT, Velmurugan A, Neeravi A, Kumar Daniel JL, Vidal JE, Kompithra RZ, Verghese VP, Veeraraghavan B, Robinson DA. Pneumococcal population genomics changes during the early time period of conjugate vaccine uptake in southern India. Microb Genom 2024; 10:001191. [PMID: 38315173 PMCID: PMC10926699 DOI: 10.1099/mgen.0.001191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 01/22/2024] [Indexed: 02/07/2024] Open
Abstract
Streptococcus pneumoniae is a major cause of invasive disease of young children in low- and middle-income countries. In southern India, pneumococcal conjugate vaccines (PCVs) that can prevent invasive pneumococcal disease began to be used more frequently after 2015. To characterize pneumococcal evolution during the early time period of PCV uptake in southern India, genomes were sequenced and selected characteristics were determined for 402 invasive isolates collected from children <5 years of age during routine surveillance from 1991 to 2020. Overall, the prevalence and diversity of vaccine type (VT) and non-vaccine type (NVT) isolates did not significantly change post-uptake of PCV. Individually, serotype 1 and global pneumococcal sequence cluster (GPSC or strain lineage) 2 significantly decreased, whereas serotypes 6B, 9V and 19A and GPSCs 1, 6, 10 and 23 significantly increased in proportion post-uptake of PCV. Resistance determinants to penicillin, erythromycin, co-trimoxazole, fluoroquinolones and tetracycline, and multidrug resistance significantly increased in proportion post-uptake of PCV and especially among VT isolates. Co-trimoxazole resistance determinants were common pre- and post-uptake of PCV (85 and 93 %, respectively) and experienced the highest rates of recombination in the genome. Accessory gene frequencies were seen to be changing by small amounts across the frequency spectrum specifically among VT isolates, with the largest changes linked to antimicrobial resistance determinants. In summary, these results indicate that as of 2020 this pneumococcal population was not yet approaching a PCV-induced equilibrium and they highlight changes related to antimicrobial resistance. Augmenting PCV coverage and prudent use of antimicrobials are needed to counter invasive pneumococcal disease in this region.
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Affiliation(s)
- Iftekhar M. Rafiqullah
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Rosemol Varghese
- Department of Clinical Microbiology, Christian Medical College and Hospital, Vellore, India
| | - K. Taylor Hellmann
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Aravind Velmurugan
- Department of Clinical Microbiology, Christian Medical College and Hospital, Vellore, India
| | - Ayyanraj Neeravi
- Department of Clinical Microbiology, Christian Medical College and Hospital, Vellore, India
| | | | - Jorge E. Vidal
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA
- Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS, USA
| | - Rajeev Z. Kompithra
- Department of Child Health, Christian Medical College and Hospital, Vellore, India
| | - Valsan P. Verghese
- Department of Child Health, Christian Medical College and Hospital, Vellore, India
| | - Balaji Veeraraghavan
- Department of Clinical Microbiology, Christian Medical College and Hospital, Vellore, India
| | - D. Ashley Robinson
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA
- Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS, USA
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12
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Papachristidou S, Lapea V, Charisi M, Kourkouni E, Kousi D, Xirogianni A, Dedousi O, Papaconstadopoulos I, Eleftheriou E, Krepis P, Pasparaki S, Pantalos G, Doudoulakakis A, Bozavoutoglou E, Daskalaki M, Kostaridou-Nikolopoulou S, Tzanakaki G, Spoulou V, Tsolia M. A multicenter study on the epidemiology of complicated parapneumonic effusion in the era of currently available pneumococcal conjugate vaccines. Vaccine 2023; 41:6727-6733. [PMID: 37805358 DOI: 10.1016/j.vaccine.2023.10.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 09/27/2023] [Accepted: 10/02/2023] [Indexed: 10/09/2023]
Abstract
BACKGROUND Parapneumonic effusion (PPE) is a common complication of pneumonia. Streptococcus pneumoniae is the most common cause of bacterial pneumonia. A reduction in pneumonia hospitalizations has been observed since the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Despite this apparent benefit, an increase in the incidence of PPE was recorded in some countries following PCV7 implementation. As the 13-valent pneumococcal conjugate vaccine (PCV13) was expected to provide a wider protection against PPE, the aim of the present study was to evaluate the impact of PCV13 introduction on the epidemiology of complicated parapneumonic effusion (c-PPE) among children in the Athens greater area. METHODS All cases of community-acquired pneumonia (CAP) with PPE requiring chest tube insertion (complicated PPE, c-PPE) hospitalized in the 3 public Children's hospitals in Athens between 01/01/2004 and 31/12/2019 were included in the study. RESULTS A total of 426 cases of c-PPE associated with pneumonia were recorded of which 198 were admitted during 2004-2010 (period A, prePCV13/PCV -7 introduction period) and 228 during 2011-2018 (period B, post - PCV13 period). A definite bacterial etiology was established in 44.4 % of all cases and of those 25.4 % were caused by S. pneumoniae. An increasing trend in c-PPE incidence was observed during period A; although, a significant decrease on c-PPE annual rates was observed during the period B (p = 0.011), a remarkable increase in serotype 3 cases was recorded. CONCLUSION A decreasing time trend in c-PPE cases among children was shown after the introduction of PCV13 in our area. However, serotype 3 is nowadays a common cause of PPE. Hence, continuous surveillance is imperative in order to follow c-PPE epidemiology over time.
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Affiliation(s)
- Smaragda Papachristidou
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece.
| | - Vasiliki Lapea
- First Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aghia Sophia Children's Hospital, Athens, Greece
| | - Martha Charisi
- Department of Paediatrics, Penteli Children's Hospital, Athens, Greece
| | - Eleni Kourkouni
- Collaborative Center for Clinical Epidemiology and Outcomes Research (CLEO), Athens, Greece
| | - Dimitra Kousi
- Collaborative Center for Clinical Epidemiology and Outcomes Research (CLEO), Athens, Greece
| | - Athanasia Xirogianni
- National Meningitis Reference Laboratory, Dept of Public Health Policy, School of Public Health, University of West Attica, Athens, Greece
| | - Olga Dedousi
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
| | - Irene Papaconstadopoulos
- First Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aghia Sophia Children's Hospital, Athens, Greece
| | - Eirini Eleftheriou
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
| | - Panagiotis Krepis
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
| | - Sophia Pasparaki
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
| | - Georgios Pantalos
- Pediatric Intensive Care Unit, Penteli's Children Hospital, Penteli, Greece
| | | | | | - Maria Daskalaki
- Microbiology Laboratory, Penteli Children's Hospital, Athens, Greece
| | | | - Georgina Tzanakaki
- National Meningitis Reference Laboratory, Dept of Public Health Policy, School of Public Health, University of West Attica, Athens, Greece
| | - Vana Spoulou
- First Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aghia Sophia Children's Hospital, Athens, Greece
| | - Maria Tsolia
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
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13
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Battista M, Hoffmann B, Bachelot Y, Zimmermann L, Teuber L, Jost A, Linde S, Westermann M, Müller MM, Slevogt H, Hammerschmidt S, Figge MT, Vilhena C, Zipfel PF. The role of pneumococcal extracellular vesicles on the pathophysiology of the kidney disease hemolytic uremic syndrome. mSphere 2023; 8:e0014223. [PMID: 37358300 PMCID: PMC10449520 DOI: 10.1128/msphere.00142-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 04/20/2023] [Indexed: 06/27/2023] Open
Abstract
Streptococcus pneumoniae-induced hemolytic uremic syndrome (Sp-HUS) is a kidney disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. This disease is frequently underdiagnosed and its pathophysiology is poorly understood. In this work, we compared clinical strains, isolated from infant Sp-HUS patients, with a reference pathogenic strain D39, for host cytotoxicity and further explored the role of Sp-derived extracellular vesicles (EVs) in the pathogenesis of an HUS infection. In comparison with the wild-type strain, pneumococcal HUS strains caused significant lysis of human erythrocytes and increased the release of hydrogen peroxide. Isolated Sp-HUS EVs were characterized by performing dynamic light-scattering microscopy and proteomic analysis. Sp-HUS strain released EVs at a constant concentration during growth, yet the size of the EVs varied and several subpopulations emerged at later time points. The cargo of the Sp-HUS EVs included several virulence factors at high abundance, i.e., the ribosomal subunit assembly factor BipA, the pneumococcal surface protein A, the lytic enzyme LytC, several sugar utilization, and fatty acid synthesis proteins. Sp-HUS EVs strongly downregulated the expression of the endothelial surface marker platelet endothelial cell adhesion molecule-1 and were internalized by human endothelial cells. Sp-HUS EVs elicited the release of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6) and chemokines (CCL2, CCL3, CXCL1) by human monocytes. These findings shed new light on the overall function of Sp-EVs, in the scope of infection-mediated HUS, and suggest new avenues of research for exploring the usefulness of Sp-EVs as therapeutic and diagnostic targets. IMPORTANCE Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS) is a serious and underdiagnosed deadly complication of invasive pneumococcal disease. Despite the introduction of the pneumococcal vaccine, cases of Sp-HUS continue to emerge, especially in children under the age of 2. While a lot has been studied regarding pneumococcal proteins and their role on Sp-HUS pathophysiology, little is known about the role of extracellular vesicles (EVs). In our work, we isolate and initially characterize EVs from a reference pathogenic strain (D39) and a strain isolated from a 2-year-old patient suffering from Sp-HUS. We demonstrate that despite lacking cytotoxicity toward human cells, Sp-HUS EVs are highly internalized by endothelial cells and can trigger cytokine and chemokine production in monocytes. In addition, this work specifically highlights the distinct morphological characteristics of Sp-HUS EVs and their unique cargo. Overall, this work sheds new light into potentially relevant players contained in EVs that might elucidate about pneumococcal EVs biogenesis or pose as interesting candidates for vaccine design.
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Affiliation(s)
- Miriana Battista
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
| | - Bianca Hoffmann
- Applied Systems Biology, HKI-Center for Systems Biology of Infection, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany
| | - Yann Bachelot
- Applied Systems Biology, HKI-Center for Systems Biology of Infection, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany
| | - Lioba Zimmermann
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
| | - Laura Teuber
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
| | - Aurélie Jost
- Microverse Imaging Center, Cluster of Excellence “Balance of the Microverse,” Friedrich Schiller University, Jena, Germany
| | - Susanne Linde
- Center for Electron Microscopy, Jena University Hospital, Jena, Germany
| | - Martin Westermann
- Center for Electron Microscopy, Jena University Hospital, Jena, Germany
| | - Mario M. Müller
- Septomics Research Center, Jena University Hospital, Jena, Germany
| | - Hortense Slevogt
- Septomics Research Center, Jena University Hospital, Jena, Germany
| | - Sven Hammerschmidt
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Marc Thilo Figge
- Applied Systems Biology, HKI-Center for Systems Biology of Infection, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany
- Faculty of Biological Sciences, Institute of Microbiology, Friedrich Schiller University, Jena, Germany
| | - Cláudia Vilhena
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
| | - Peter F. Zipfel
- Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
- Faculty of Biological Sciences, Institute of Microbiology, Friedrich Schiller University, Jena, Germany
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14
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Puzia W, Gawor J, Gromadka R, Żuchniewicz K, Wróbel-Pawelczyk I, Ronkiewicz P, Gołębiewska A, Hryniewicz W, Sadowy E, Skoczyńska A. Highly Resistant Serotype 19A Streptococcus pneumoniae of the GPSC1/CC320 Clone from Invasive Infections in Poland Prior to Antipneumococcal Vaccination of Children. Infect Dis Ther 2023; 12:2017-2037. [PMID: 37442903 PMCID: PMC10505132 DOI: 10.1007/s40121-023-00842-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 06/23/2023] [Indexed: 07/15/2023] Open
Abstract
INTRODUCTION The introduction of pneumococcal conjugate vaccines (PCV) into the national immunization programs (NIPs) has significantly reduced the number of pneumococcal infections. However, infections caused by isolates of non-vaccine serotypes (NVT) started spreading shortly thereafter and strains of NVT 19A have become the main cause of invasive pneumococcal disease burden worldwide. The aim of the study was to characterize serotype 19A invasive pneumococci of GPSC1/CC320 circulating in Poland before the introduction of PCV into the Polish NIP in 2017 and to compare them to isolates from other countries where PCVs were implemented much earlier than in Poland. METHODS All the GPSC1/CC320 isolates were analyzed by serotyping, susceptibility testing, and whole genome sequencing followed by analyses of resistome, virulome, and core genome multilocus sequence typing (cgMLST), including comparative analysis with isolates with publicly accessible genomic sequences (PubMLST). RESULTS During continuous surveillance the NRCBM collected 4237 invasive Streptococcus pneumoniae isolates between 1997 and 2016, including 200 isolates (4.7%) of serotype 19A. The most prevalent among 19A pneumococci were highly resistant representatives of Global Pneumococcal Sequence Cluster 1/Clonal Complex 320, GPSC1/CC320 (n = 97, 48.5%). Isolates of GPSC1/CC320 belonged to three sequence types (STs): ST320 (75.2%) ST4768 (23.7%), and ST15047 (1.0%), which all represented the 19A-III cps subtype and had complete loci for both PI-1 and PI-2 pili types. On the basis of the cgMLST analysis the majority of Polish GPSC1/CC320 isolates formed a group clearly distinct from pneumococci of this clone observed in other countries. CONCLUSION Before introduction of PCV in the Polish NIP we noticed an unexpected increase of serotype 19A in invasive pneumococcal infections, with the most common being representatives of highly drug-resistant GPSC1/CC320 clone, rarely identified in Europe both before and even after PCV introduction.
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Affiliation(s)
- Weronika Puzia
- Department of Epidemiology and Clinical Microbiology, National Reference Centre for Bacterial Meningitis, National Medicines Institute, Chełmska 30/34 Str., 00-725, Warsaw, Poland
- DNA Sequencing and Synthesis Facility, Institute of Biochemistry and Biophysics PAS, Pawińskiego 5a Str., 02-106, Warsaw, Poland
| | - Jan Gawor
- DNA Sequencing and Synthesis Facility, Institute of Biochemistry and Biophysics PAS, Pawińskiego 5a Str., 02-106, Warsaw, Poland
| | - Robert Gromadka
- DNA Sequencing and Synthesis Facility, Institute of Biochemistry and Biophysics PAS, Pawińskiego 5a Str., 02-106, Warsaw, Poland
| | - Karolina Żuchniewicz
- DNA Sequencing and Synthesis Facility, Institute of Biochemistry and Biophysics PAS, Pawińskiego 5a Str., 02-106, Warsaw, Poland
| | - Izabela Wróbel-Pawelczyk
- Department of Epidemiology and Clinical Microbiology, National Reference Centre for Bacterial Meningitis, National Medicines Institute, Chełmska 30/34 Str., 00-725, Warsaw, Poland
| | - Patrycja Ronkiewicz
- Department of Epidemiology and Clinical Microbiology, National Reference Centre for Bacterial Meningitis, National Medicines Institute, Chełmska 30/34 Str., 00-725, Warsaw, Poland
| | - Agnieszka Gołębiewska
- Department of Epidemiology and Clinical Microbiology, National Reference Centre for Bacterial Meningitis, National Medicines Institute, Chełmska 30/34 Str., 00-725, Warsaw, Poland
| | - Waleria Hryniewicz
- Department of Epidemiology and Clinical Microbiology, National Reference Centre for Bacterial Meningitis, National Medicines Institute, Chełmska 30/34 Str., 00-725, Warsaw, Poland
| | - Ewa Sadowy
- Department of Molecular Microbiology, National Medicines Institute, Chełmska 30/34 Str., 00-725, Warsaw, Poland
| | - Anna Skoczyńska
- Department of Epidemiology and Clinical Microbiology, National Reference Centre for Bacterial Meningitis, National Medicines Institute, Chełmska 30/34 Str., 00-725, Warsaw, Poland.
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15
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Maruhn K, Itzek A, Imoehl M, van der Linden M. A simple PCR assay for the identification of the novel Streptococcus pneumoniae serotype 7D. J Med Microbiol 2023; 72. [PMID: 37552048 DOI: 10.1099/jmm.0.001739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/09/2023] Open
Abstract
The identification of the novel pneumococcal serotype 7D by Neufeld quellung reaction requires significant expertise. To circumvent this, we developed a simple serotype-specific PCR method to discriminate serotype 7D from the closely related serotypes 7C, 7B and 40. The established PCR was validated with the strain collection of the German National Reference Center for Streptococci (GNRCS). However, no isolate initially assigned as serotype 7B, 7C or 40 was identified as serotype 7D.
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Affiliation(s)
- Karsten Maruhn
- National Reference Center for Streptococci, Institute of Medical Microbiology, University Hospital RWTH, Aachen, Germany
- Laboratory Diagnostic Center, University Hospital RWTH Aachen, Aachen, Germany
| | - Andreas Itzek
- National Reference Center for Streptococci, Institute of Medical Microbiology, University Hospital RWTH, Aachen, Germany
| | - Matthias Imoehl
- Laboratory Diagnostic Center, University Hospital RWTH Aachen, Aachen, Germany
| | - Mark van der Linden
- National Reference Center for Streptococci, Institute of Medical Microbiology, University Hospital RWTH, Aachen, Germany
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16
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Ramgopal S, Cotter JM, Navanandan N, Shah SS, Ruddy RM, Ambroggio L, Florin TA. Viral Detection Is Associated With Severe Disease in Children With Suspected Community-Acquired Pneumonia. Pediatr Emerg Care 2023; 39:465-469. [PMID: 37308159 PMCID: PMC11311203 DOI: 10.1097/pec.0000000000002982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
OBJECTIVE To evaluate the role of virus detection on disease severity among children presenting to the emergency department (ED) with suspected community-acquired pneumonia (CAP). METHODS We performed a single-center prospective study of children presenting to a pediatric ED with signs and symptoms of a lower respiratory tract infection and who had a chest radiograph performed for suspected CAP. We included patients who had virus testing, with results classified as negative for virus, human rhinovirus, respiratory syncytial virus (RSV), influenza, and other viruses. We evaluated the association between virus detection and disease severity using a 4-tiered measure of disease severity based on clinical outcomes, ranging from mild ( discharged from the ED) to severe (receipt of positive-pressure ventilation, vasopressors, thoracostomy tube placement, or extracorporeal membrane oxygenation, intensive care unit admission, diagnosis of severe sepsis or septic shock, or death) in models adjusted for age, procalcitonin, C-reactive protein, radiologist interpretation of the chest radiograph, presence of wheeze, fever, and provision of antibiotics. RESULTS Five hundred seventy-three patients were enrolled in the parent study, of whom viruses were detected in 344 (60%), including 159 (28%) human rhinovirus, 114 (20%) RSV, and 34 (6%) with influenza. In multivariable models, viral infections were associated with increasing disease severity, with the greatest effect noted with RSV (adjusted odds ratio [aOR], 2.50; 95% confidence interval [CI], 1.30-4.81) followed by rhinovirus (aOR, 2.18; 95% CI, 1.27-3.76). Viral detection was not associated with increased severity among patients with radiographic pneumonia (n = 223; OR, 1.82; 95% CI, 0.87-3.87) but was associated with severity among patients without radiographic pneumonia (n = 141; OR, 2.51; 95% CI, 1.40-4.59). CONCLUSIONS The detection of a virus in the nasopharynx was associated with more severe disease compared with no virus; this finding persisted after adjustment for age, biomarkers, and radiographic findings. Viral testing may assist with risk stratification of patients with lower respiratory tract infections.
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Affiliation(s)
- Sriram Ramgopal
- Division of Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Jillian M. Cotter
- Section of Pediatric Hospital Medicine, Children’s Hospital Colorado, Department of Pediatrics, University of Colorado, Aurora, CO
| | - Nidhya Navanandan
- Section of Emergency Medicine, Children’s Hospital Colorado, Department of Pediatrics, University of Colorado, Aurora, CO
| | - Samir S. Shah
- Divisions of Hospital Medicine and Infectious Diseases, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH
| | - Richard M. Ruddy
- Division of Emergency Medicine, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH
| | - Lilliam Ambroggio
- Section of Pediatric Hospital Medicine, Children’s Hospital Colorado, Department of Pediatrics, University of Colorado, Aurora, CO
- Section of Emergency Medicine, Children’s Hospital Colorado, Department of Pediatrics, University of Colorado, Aurora, CO
| | - Todd A. Florin
- Division of Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
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17
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Adam HJ, Karlowsky JA, Baxter MR, Schellenberg J, Golden AR, Martin I, Demczuk W, Mulvey MR, Zhanel GG. Analysis of MDR in the predominant Streptococcus pneumoniae serotypes in Canada: the SAVE study, 2011-2020. J Antimicrob Chemother 2023; 78:i17-i25. [PMID: 37130586 DOI: 10.1093/jac/dkad066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/04/2023] Open
Abstract
OBJECTIVES To investigate the levels of MDR in the predominant serotypes of invasive Streptococcus pneumoniae isolated in Canada over a 10 year period. METHODS All isolates were serotyped and had antimicrobial susceptibility testing performed, in accordance with CLSI guidelines (M07-11 Ed., 2018). Complete susceptibility profiles were available for 13 712 isolates. MDR was defined as resistance to three or more classes of antimicrobial agents (penicillin MIC ≥2 mg/L defined as resistant). Serotypes were determined by Quellung reaction. RESULTS In total, 14 138 invasive isolates of S. pneumoniae were tested in the SAVE study (S. pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada), a collaboration between the Canadian Antimicrobial Resistance Alliance and Public Health Agency of Canada-National Microbiology Laboratory. The rate of MDR S. pneumoniae in SAVE was 6.6% (902/13 712). Annual rates of MDR S. pneumoniae decreased between 2011 and 2015 (8.5% to 5.7%) and increased between 2016 and 2020 (3.9% to 9.4%). Serotypes 19A and 15A were the most common serotypes demonstrating MDR (25.4% and 23.5% of the MDR isolates, respectively); however, the serotype diversity index increased from 0.7 in 2011 to 0.9 in 2020 with a statistically significant linear increasing trend (P < 0.001). In 2020, MDR isolates were frequently serotypes 4 and 12F in addition to serotypes 15A and 19A. In 2020, 27.3%, 45.5%, 50.5%, 65.7% and 68.7% of invasive MDR S. pneumoniae were serotypes included in the PCV10, PCV13, PCV15, PCV20 and PPSV23 vaccines, respectively. CONCLUSIONS Although current vaccine coverage of MDR S. pneumoniae in Canada is high, the increasing diversity of serotypes observed among the MDR isolates highlights the ability of S. pneumoniae to rapidly evolve.
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Affiliation(s)
- Heather J Adam
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- Clinical Microbiology, Shared Health, MS673-820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada
| | - James A Karlowsky
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- Clinical Microbiology, Shared Health, MS673-820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada
| | - Melanie R Baxter
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - John Schellenberg
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - Alyssa R Golden
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
| | - Irene Martin
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
| | - Walter Demczuk
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
| | - Michael R Mulvey
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada
| | - George G Zhanel
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
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Alford MA, Karlowsky JA, Adam HJ, Baxter MR, Schellenberg J, Golden AR, Martin I, Demczuk W, Mulvey MR, Zhanel GG. Antimicrobial susceptibility testing of invasive isolates of Streptococcus pneumoniae from Canadian patients: the SAVE study, 2011-2020. J Antimicrob Chemother 2023; 78:i8-i16. [PMID: 37130584 DOI: 10.1093/jac/dkad065] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/04/2023] Open
Abstract
OBJECTIVES To assess the antimicrobial susceptibility of 14 138 invasive Streptococcus pneumoniae isolates collected in Canada from 2011 to 2020. METHODS Antimicrobial susceptibility testing was performed using the CLSI M07 broth microdilution reference method. MICs were interpreted using 2022 CLSI M100 breakpoints. RESULTS In 2020, 90.1% and 98.6% of invasive pneumococci were penicillin-susceptible when MICs were interpreted using CLSI meningitis or oral and non-meningitis breakpoints, respectively; 96.9% (meningitis breakpoint) and 99.5% (non-meningitis breakpoint) of isolates were ceftriaxone-susceptible, and 99.9% were levofloxacin-susceptible. Numerically small, non-temporal, but statistically significant differences (P < 0.05) in the annual percentage of isolates susceptible to four of the 13 agents tested was observed across the 10-year study: chloramphenicol (4.4% difference), trimethoprim-sulfamethoxazole (3.9%), penicillin (non-meningitis breakpoint, 2.7%) and ceftriaxone (meningitis breakpoint, 2.7%; non-meningitis breakpoint, 1.2%). During the same period, annual differences in percent susceptible values for penicillin (meningitis and oral breakpoints) and all other agents did not achieve statistical significance. The percentage of isolates with an MDR phenotype (resistance to ≥3 antimicrobial classes) in 2011 and 2020 (8.5% and 9.4%) was not significantly different (P = 0.109), although there was a significant interim decrease observed between 2011 and 2015 (P < 0.001) followed by a significant increase between 2016 and 2020 (P < 0.001). Statistically significant associations were observed between resistance rates to most antimicrobial agents included in the MDR analysis (penicillin, clarithromycin, clindamycin, doxycycline, trimethoprim/sulfamethoxazole and chloramphenicol) and patient age, specimen source, geographic location in Canada or concurrent resistance to penicillin or clarithromycin, but not biological sex of patients. Given the large isolate collection studied, statistical significance did not necessarily imply clinical or public health significance in some analyses. CONCLUSIONS Invasive pneumococcal isolates collected in Canada from 2011 to 2020 generally exhibited consistent in vitro susceptibility to commonly tested antimicrobial agents.
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Affiliation(s)
- Morgan A Alford
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - James A Karlowsky
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- Clinical Microbiology, Shared Health, MS673-820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada
| | - Heather J Adam
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- Clinical Microbiology, Shared Health, MS673-820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada
| | - Melanie R Baxter
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - John Schellenberg
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - Alyssa R Golden
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
| | - Irene Martin
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
| | - Walter Demczuk
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
| | - Michael R Mulvey
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
| | - George G Zhanel
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
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Hawkins PA, Chochua S, Lo SW, Belman S, Antonio M, Kwambana-Adams B, von Gottberg A, du Plessis M, Cornick J, Beall B, Breiman RF, Bentley SD, McGee L. A global genomic perspective on the multidrug-resistant Streptococcus pneumoniae 15A-CC63 sub-lineage following pneumococcal conjugate vaccine introduction. Microb Genom 2023; 9. [PMID: 37083600 DOI: 10.1099/mgen.0.000998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2023] Open
Abstract
The introduction of pneumococcal conjugate vaccines (PCV7, PCV10, PCV13) around the world has proved successful in preventing invasive pneumococcal disease. However, immunization against Streptococcus pneumoniae has led to serotype replacement by non-vaccine serotypes, including serotype 15A. Clonal complex 63 (CC63) is associated with many serotypes and has been reported in association with 15A after introduction of PCVs. A total of 865 CC63 isolates were included in this study, from the USA (n=391) and a global collection (n=474) from 1998-2019 and 1995-2018, respectively. We analysed the genomic sequences to identify serotypes and penicillin-binding protein (PBP) genes 1A, 2B and 2X, and other resistance determinants, to predict minimum inhibitory concentrations (MICs) against penicillin, erythromycin, clindamycin, co-trimoxazole and tetracycline. We conducted phylogenetic and spatiotemporal analyses to understand the evolutionary history of the 15A-CC63 sub-lineage. Overall, most (89.5 %, n=247) pre-PCV isolates in the CC63 cluster belonged to serotype 14, with 15A representing 6.5 % of isolates. Conversely, serotype 14 isolates represented 28.2 % of post-PCV CC63 isolates (n=618), whilst serotype 15A isolates represented 65.4 %. Dating of the CC63 lineage determined the most recent common ancestor emerged in the 1980s, suggesting the 15A-CC63 sub-lineage emerged from its closest serotype 14 ancestor prior to the development of pneumococcal vaccines. This sub-lineage was predominant in the USA, Israel and China. Multidrug resistance (to three or more drug classes) was widespread among isolates in this sub-lineage. We show that the CC63 lineage is globally distributed and most of the isolates are penicillin non-susceptible, and thus should be monitored.
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Affiliation(s)
- Paulina A Hawkins
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Sopio Chochua
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Stephanie W Lo
- Parasites and Microbes, Wellcome Sanger Institute, Hinxton, Cambridge, UK
| | - Sophie Belman
- Parasites and Microbes, Wellcome Sanger Institute, Hinxton, Cambridge, UK
| | - Martin Antonio
- MRC Unit The Gambia, London School of Hygiene and Tropical Medicine, Banjul, The Gambia
| | - Brenda Kwambana-Adams
- MRC Unit The Gambia, London School of Hygiene and Tropical Medicine, Banjul, The Gambia
| | - Anne von Gottberg
- National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa
- School of Pathology, University of the Witwatersrand, Johannesburg, South Africa
| | - Mignon du Plessis
- National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa
- School of Pathology, University of the Witwatersrand, Johannesburg, South Africa
| | - Jen Cornick
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
| | - Bernard Beall
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Robert F Breiman
- Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Stephen D Bentley
- Parasites and Microbes, Wellcome Sanger Institute, Hinxton, Cambridge, UK
| | - Lesley McGee
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Oligopeptide Transporters of Nonencapsulated Streptococcus pneumoniae Regulate CbpAC and PspA Expression and Reduce Complement-Mediated Clearance. mBio 2023; 14:e0332522. [PMID: 36625598 PMCID: PMC9973307 DOI: 10.1128/mbio.03325-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Streptococcus pneumoniae colonizes the human nasopharynx and causes several diseases. Pneumococcal vaccines target the polysaccharide capsule and prevent most serious disease, but there has been an increase in the prevalence of nonencapsulated S. pneumoniae (NESp). Previously, it was thought that a capsule was necessary to cause invasive disease. NESp strains expressing the oligopeptide transporters AliC and AliD have been isolated from patients with invasive disease. The AliC and AliD oligopeptide transporters regulate the expression of several genes, including choline binding protein AC (CbpAC) (a homolog of PspA), which aids in reducing C3b deposition. It is hypothesized that by altering CbpAC expression, AliC and AliD provide protection from classical complement-mediated clearance by reducing C-reactive protein (CRP) binding. Our study demonstrates that AliC and AliD regulate CbpAC expression in NESp and that AliD found in certain serotypes of encapsulated strains regulates PspA expression. C3b deposition was increased in the NESp ΔaliD and encapsulated mutants in comparison to the wild type. NESp strains expressing AliC and AliD have a significant decrease in C1q and CRP deposition in comparison to the ΔaliC ΔaliD mutant. The complement protein C1q is required for NESp clearance in a murine model and increases opsonophagocytosis. By regulating CbpAC expression, NESp inhibits CRP binding to the bacterial surface and blocks classical complement activation, leading to greater systemic survival and virulence. Due to the increase in the prevalence of NESp, it is important to gain a better understanding of NESp virulence mechanisms that aid in establishing disease and persistence within a host by avoiding clearance by the immune system. IMPORTANCE Streptococcus pneumoniae (pneumococcus) can cause a range of diseases. Although there is a robust pneumococcal vaccination program that reduces invasive pneumococcal disease by targeting various polysaccharide capsules, there has been an increase in the isolation of nonvaccine serotypes and nonencapsulated S. pneumoniae (NESp) strains. While most studies of pneumococcal pathogenesis have focused on encapsulated strains, there is little understanding of how NESp causes disease. NESp lacks a protective capsule but contains novel genes, such as aliC and aliD, which have been shown to regulate the expression of numerous genes and to be required for NESp virulence and immune evasion. Furthermore, NESp strains have high transformation efficiencies and harbor resistance to multiple drugs. This could be deleterious to current treatment strategies employed for pneumococcal disease as NESp can be a reservoir of drug resistance genes. Therefore, deciphering how NESp survives within a host and facilitates disease is a necessity that will allow the fabrication of improved, broad-spectrum treatments and preventatives against pneumococcal disease. Our study provides a better understanding of NESp virulence mechanisms during host-pathogen interactions through the examination of genes directly regulated by the NESp proteins AliC and AliD.
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Allicock OM, York A, Waghela P, Yolda-Carr D, Weinberger DM, Wyllie AL. Impact of Temporary Storage Conditions on the Viability of Streptococcus pneumoniae in Saliva. mSphere 2022; 7:e0033122. [PMID: 36409104 PMCID: PMC9769876 DOI: 10.1128/msphere.00331-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 11/03/2022] [Indexed: 11/23/2022] Open
Abstract
Nasopharyngeal swabs are considered the gold-standard sample type for the detection of Streptococcus pneumoniae carriage, but recent studies have demonstrated the utility of saliva in improving the detection of carriage in adults. Saliva is generally collected in its raw, unsupplemented state, unlike nasopharyngeal swabs, which are collected into stabilizing transport media. Few data exist regarding the stability of pneumococci in unsupplemented saliva during transport and laboratory storage. We therefore evaluated the effect of storage conditions on the detection of pneumococci in saliva samples using strains representing eight pneumococcal serotypes. The bacteria were spiked into raw saliva from asymptomatic individuals, and we assessed sample viability after storage at 4°C, room temperature, and 30°C for up to 72 h; at 40°C for 24 h; and following three freeze-thaw cycles. We observed little decrease in pneumococcal detection following culture enrichment and quantitative PCR (qPCR) detection of the piaB and lytA genes compared to testing fresh samples, indicating the prolonged viability of pneumococci in neat saliva samples. This sample stability makes saliva a viable sample type for pneumococcal carriage studies conducted in remote or low-resource settings and provides insight into the effect of the storage of saliva samples in the laboratory. IMPORTANCE For pneumococcal carriage studies, saliva is a sample type that can overcome some of the issues typically seen with nasopharyngeal and oropharyngeal swabs. Understanding the limitations of saliva as a sample type is important for maximizing its use. This study sought to better understand how different storage conditions and freeze-thaw cycles affect pneumococcal survival over time. These findings support the use of saliva as an alternative sample type for pneumococcal carriage studies, particularly in remote or low-resource settings with reduced access to health care facilities.
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Affiliation(s)
- Orchid M. Allicock
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
| | - Anna York
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
| | - Pari Waghela
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
| | - Devyn Yolda-Carr
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
| | - Daniel M. Weinberger
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
| | - Anne L. Wyllie
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA
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22
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Streptococcus pneumoniae vaccination strategies and its expected impact on penicillin non-susceptibility in children under the age of five: Let's recap! Vaccine X 2022; 11:100170. [PMID: 35620569 PMCID: PMC9127579 DOI: 10.1016/j.jvacx.2022.100170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 12/23/2021] [Accepted: 05/09/2022] [Indexed: 11/22/2022] Open
Abstract
The efficacy of PCVs currently used in children under 5 years of age is threatened by the emergence of invasive and resistant non-vaccine serotypes worldwide. Resistant NVT strains are emerging in IPD in children < 5 years mainly serotypes 24F, 15A, 11A and 33F along with serotype 19A in PCV-10 settings. Continuous surveillance is necessary in IPD in children under five to monitor the long-term effect of PCV-10 and PCV-13 on penicillin resistance trends. The impact of pneumococcal conjugate vaccines (PCVs) on invasive pneumococcal disease (IPD) burden has been extensively studied in children aged<5 years; however, a pooled estimation of the effect of PCVs on penicillin non-susceptible pneumococci (PNSP) has not yet been performed. We aimed to identify whether the introduction of PCV-10 and PCV-13 had led to the decrease of the overall PNSP rate in children < 5 years. We conducted a systematic review of published surveillance studies reporting the rate of PNSP rates in children < 5 in countries where PCV10/13 were introduced. The overall observed trend onwards the introduction of PCV-10 and PCV-13 is a decrease in PNSP among children < 5 years in surveillance sites located in PCV-13 countries. We identified an increase of PNSP rates (serotype 19A) in PCV-10 settings. Resistant NVT strains are emerging in IPD in children < 5 years mainly serotypes 24F, 15A, 11A and 33F along with serotype 19A in PCV-10 settings. Continuous surveillance is necessary in IPD in children under five to monitor the long-term effect of PCV-10 and PCV-13 on penicillin resistance trends.
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23
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Pike J, Leidner AJ, Chesson H, Stoecker C, Grosse SD. Data-Related Challenges in Cost-Effectiveness Analyses of Vaccines. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2022; 20:457-465. [PMID: 35138601 PMCID: PMC9233035 DOI: 10.1007/s40258-022-00718-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/16/2022] [Indexed: 05/13/2023]
Abstract
Cost-effectiveness analyses (CEAs) are often prepared to quantify the expected economic value of potential vaccination strategies. Estimated outcomes and costs of vaccination strategies depend on numerous data inputs or assumptions, including estimates of vaccine efficacy and disease incidence in the absence of vaccination. Limitations in epidemiologic data can meaningfully affect both CEA estimates and the interpretation of those results by groups involved in vaccination policy decisions. Developers of CEAs should be transparent with regard to the ambiguity and uncertainty associated with epidemiologic information that is incorporated into their models. We describe selected data-related challenges to conducting CEAs for vaccination strategies, including generalizability of estimates of vaccine effectiveness, duration and functional form of vaccine protection that can change over time, indirect (herd) protection, and serotype replacement. We illustrate how CEA estimates can be sensitive to variations in specific epidemiologic assumptions, with examples from CEAs conducted for the USA that assessed vaccinations against human papillomavirus and pneumococcal disease. These challenges are certainly not limited to these two case studies and may be relevant to other vaccines.
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Affiliation(s)
- Jamison Pike
- Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, 1600 Clifton Road NE, Atlanta, GA, 30329, USA.
| | - Andrew J Leidner
- Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, 1600 Clifton Road NE, Atlanta, GA, 30329, USA
| | - Harrell Chesson
- Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Atlanta, GA, USA
| | - Charles Stoecker
- School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA
| | - Scott D Grosse
- Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Atlanta, GA, USA
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Ricketson LJ, Bettinger JA, Sadarangani M, Halperin SA, Kellner JD. Vaccine effectiveness of the 7-valent and 13-valent pneumococcal conjugate vaccines in Canada: An IMPACT study. Vaccine 2022; 40:2733-2740. [PMID: 35351324 DOI: 10.1016/j.vaccine.2022.03.048] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 03/18/2022] [Accepted: 03/20/2022] [Indexed: 11/26/2022]
Abstract
We used an indirect cohort analysis in children under 5 years-old from 2002 to 2018 to examine vaccine effectiveness (VE) of the 7-valent pneumococcal conjugate vaccine (PCV) (3 + 1 doses in most regions) and the 13-valent PCV (2 + 1 doses in all regions) against invasive pneumococcal disease (IPD) caused by vaccine serotypes in children in Canada. Cases were identified from the Canadian Immunization Monitoring Program ACTive (IMPACT), a national active surveillance network of 12 tertiary care pediatric hospitals that represent about 90% of tertiary care hospital beds in Canada. There were 1477 children evaluated for PCV7 VE and 489 for PCV13 VE. PCV7 VE in children with vaccination up to date for their age was 96% (95% CI: 67-99%) after a single dose and 95% (95% CI: 92-97%) after ≥2 doses. The VE was 91% (95% CI: 85-94%) in children who had received doses but were not up to date for their age. PCV13 VE in children with vaccinations up to date for their age was 55% (95% CI: 28-72%) after ≥2 doses. The PCV13-vaccine serotypes causing breakthrough IPD in children up to date for their age with 2+ doses of PCV13 were 3 (13/27, 48.2%),19A (11/27, 40.7%), and 19F (3/27, 11.1%). When serotype 3 and 19A were excluded, the VE of PCV13 against the remaining vaccine serotypes was 89% (95% CI: 64-97%) in children with ≥2 doses. The lower VE of PCV13 may be due to lower effectiveness against serotypes 3 and 19A, which could be influenced by the change in dosing schedule from 4 to 3 total doses with the introduction of PCV13, combined with vaccine uptake of 80%. However, PCV13 still provides the benefit of protection against more serotypes than PCV7, and good VE against all serotypes except 3 and 19A.
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Affiliation(s)
- Leah J Ricketson
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
| | - Julie A Bettinger
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Manish Sadarangani
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
| | - Scott A Halperin
- Canadian Centre for Vaccinology, Halifax, NS, Canada; Dalhousie University and the IWK Health Centre Dalhousie University, Halifax, NS, Canada
| | - James D Kellner
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital, Calgary Zone, Alberta Health Services, Calgary, AB, Canada.
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A novel pneumococcal surface protein K of nonencapsulated Streptococcus pneumoniae promotes transmission among littermates in an infant mouse model with influenza A virus co-infection. Infect Immun 2022; 90:e0062221. [PMID: 34978928 DOI: 10.1128/iai.00622-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
We established an infant mouse model for colonization and transmission by nonencapsulated Streptococcus pneumoniae (NESp) strains to gain important information about its virulence among children. Invasive pneumococcal diseases have decreased dramatically since the worldwide introduction of pneumococcal capsular polysaccharide vaccines. Increasing prevalence of non-vaccine serotypes including NESp has been highlighted as a challenge in treatment strategy, but the virulence of NESp is not well understood. Protective strategy against NESp colonization and transmission between children require particularly urgent evaluation. NESp lacks capsules, a major virulent factor of pneumococci, but can cause a variety of infections in children and older people. PspK, a specific surface protein of NESp, is a key factor in establishing nasal colonization. In our infant mouse model for colonization and transmission by NESp strains, NESp could establish stable nasal colonization at the same level as encapsulated serotype 6A in infant mice, and could be transmitted between littermates. Transmission was promoted by NESp surface virulence factor PspK and influenza virus co-infection. However, PspK-deletion mutants lost the ability to colonize and transmit to new hosts. Promotion of NESp transmission by influenza was due to increased susceptibility of the new hosts. PspK was a key factor not only in establishment of nasal colonization, but also in transmission to new hosts. PspK may be targeted as a new candidate vaccine for NESp infection in children.
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McDaniel LS, Swiatlo E. If Not Now, When? Nonserotype Pneumococcal Protein Vaccines. Open Forum Infect Dis 2021; 8:ofab576. [PMID: 34934775 PMCID: PMC8684483 DOI: 10.1093/ofid/ofab576] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 11/12/2021] [Indexed: 11/13/2022] Open
Abstract
The sudden emergence and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have greatly accelerated the adoption of novel vaccine strategies, which otherwise would have likely languished for years. In this light, vaccines for certain other pathogens could certainly benefit from reconsideration. One such pathogen is Streptococcus pneumoniae (pneumococcus), an encapsulated bacterium that can express >100 antigenically distinct serotypes. Current pneumococcal vaccines are based exclusively on capsular polysaccharide—either purified alone or conjugated to protein. Since the introduction of conjugate vaccines, the valence of pneumococcal vaccines has steadily increased, as has the associated complexity and cost of production. There are many pneumococcal proteins invariantly expressed across all serotypes, which have been shown to induce robust immune responses in animal models. These proteins could be readily produced using recombinant DNA technology or by mRNA technology currently used in SARS-CoV-2 vaccines. A door may be opening to new opportunities in affordable and broadly protective vaccines.
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Affiliation(s)
- Larry S McDaniel
- Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Edwin Swiatlo
- Southeast Louisiana Veterans Health Care Network, New Orleans, Louisiana, USA
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Mungall BA, Hoet B, Nieto Guevara J, Soumahoro L. A systematic review of invasive pneumococcal disease vaccine failures and breakthrough with higher-valency pneumococcal conjugate vaccines in children. Expert Rev Vaccines 2021; 21:201-214. [PMID: 34882050 DOI: 10.1080/14760584.2022.2012455] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
INTRODUCTION : The pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV or PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) protect against vaccine-serotype invasive pneumococcal disease (VT IPD). However, VT IPD can still occur in fully or partially vaccinated children (vaccine failure or breakthrough). We performed a systematic review of vaccine failures and breakthrough IPD with PCV10 and PCV13 in ≤5-year-olds. AREAS COVERED : We searched Scopus/Medline/EMBASE to retrieve articles/abstracts published between 1/2008-7/2019. We excluded reports from studies only including data from adults or children ≥6 years, exclusively assessing PCV7-vaccinated children or children with underlying comorbidities. Twenty-six reports (20 PCV13, 1 PCV10, 5 both), covering studies with various designs in six continents, using different schedules, were included. Collectively, these studies reported 469 VT IPD cases classified as vaccine failures and 403 as breakthrough. Vaccine failure and breakthrough rates were low: 8.4% and 9.3%, respectively, of all IPD in vaccinated children, consistent with the vaccines' high effectiveness. The main serotypes associated with vaccine failure or breakthrough were 19A, 3 and 19F in PCV13 studies and 14, 6B and vaccine-related 19A and 6A in PCV10 studies. EXPERT OPINION : As we move to vaccines with more serotypes, it is not only important to consider which serotypes are added, but also to monitor and address incomplete protection against specific serotypes.
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Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies. Vaccines (Basel) 2021; 9:vaccines9111338. [PMID: 34835269 PMCID: PMC8620834 DOI: 10.3390/vaccines9111338] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/12/2021] [Accepted: 11/13/2021] [Indexed: 01/24/2023] Open
Abstract
The importance of Streptococcus pneumoniae has been well established. These bacteria can colonize infants and adults without symptoms, but in some cases can spread, invade other tissues and cause disease with high morbidity and mortality. The development of pneumococcal conjugate vaccines (PCV) caused an enormous impact in invasive pneumococcal disease and protected unvaccinated people by herd effect. However, serotype replacement is a well-known phenomenon that has occurred after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and has also been reported for other PCVs. Therefore, it is possible that serotype replacement will continue to occur even with higher valence formulations, but the development of serotype-independent vaccines might overcome this problem. Alternative vaccines are under development in order to improve cost effectiveness, either using proteins or the pneumococcal whole cell. These approaches can be used as a stand-alone strategy or together with polysaccharide vaccines. Looking ahead, the next generation of pneumococcal vaccines can be impacted by the new technologies recently approved for human use, such as mRNA vaccines and viral vectors. In this paper, we will review the advantages and disadvantages of the addition of new polysaccharides in the current PCVs, mainly for low- and middle-income countries, and we will also address future perspectives.
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Narváez PO, Gomez-Duque S, Alarcon JE, Ramirez-Valbuena PC, Serrano-Mayorga CC, Lozada-Arcinegas J, Bastidas A, Gómez S, Vargas H, Feldman C, Reyes LF. Invasive pneumococcal disease burden in hospitalized adults in Bogota, Colombia. BMC Infect Dis 2021; 21:1059. [PMID: 34641809 PMCID: PMC8507327 DOI: 10.1186/s12879-021-06769-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 09/21/2021] [Indexed: 02/14/2023] Open
Abstract
Background The incidence of invasive pneumococcal disease (IPD) varies depending on a number of factors, including vaccine uptake, in both children and adults, the geographic location, and local serotype prevalence. There are limited data about the burden of Streptococcus pneumoniae (Spn), serotype distribution, and clinical characteristics of adults hospitalized due to IPD in Colombia. The objectives of this study included assessment of Spn serotype distribution, clinical characteristics, mortality, ICU admission, and the need for mechanical ventilation. Methods This was an observational, retrospective, a citywide study conducted between 2012 and 2019 in Bogotá, Colombia. We analyzed reported positive cases of IPD from 55 hospitals in a governmental pneumococcal surveillance program. Pneumococcal strains were isolated in each hospital and typified in a centralized laboratory. This is a descriptive study stratified by age and subtypes of IPD obtained through the analysis of medical records. Results A total of 310 patients with IPD were included, of whom 45.5% were female. The leading cause of IPD was pneumonia (60%, 186/310), followed by meningitis. The most frequent serotypes isolated were 19A (13.87%, 43/310) and 3 (11.94%, 37/310). The overall hospital mortality rate was 30.3% (94/310). Moreover, 52.6% (163/310 patients) were admitted to the ICU, 45.5% (141/310) required invasive mechanical ventilation and 5.1% (16/310) non-invasive mechanical ventilation. Conclusion Pneumococcal pneumonia is the most prevalent cause of IPD, with serotypes 19A and 3 being the leading cause of IPD in Colombian adults. Mortality due to IPD in adults continues to be very high. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06769-2.
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Affiliation(s)
- Paula O Narváez
- Universidad de la Sabana, Campus Puente del Común, KM 7.5 Autopista Norte de Bogotá, Chía, Colombia
| | - Salome Gomez-Duque
- Universidad de la Sabana, Campus Puente del Común, KM 7.5 Autopista Norte de Bogotá, Chía, Colombia
| | - Juan E Alarcon
- Universidad de la Sabana, Campus Puente del Común, KM 7.5 Autopista Norte de Bogotá, Chía, Colombia
| | - Paula C Ramirez-Valbuena
- Universidad de la Sabana, Campus Puente del Común, KM 7.5 Autopista Norte de Bogotá, Chía, Colombia
| | | | - Julian Lozada-Arcinegas
- Universidad de la Sabana, Campus Puente del Común, KM 7.5 Autopista Norte de Bogotá, Chía, Colombia
| | - Alirio Bastidas
- Universidad de la Sabana, Campus Puente del Común, KM 7.5 Autopista Norte de Bogotá, Chía, Colombia
| | - Sandra Gómez
- Grupo Laboratorio de Salud Pública de Bogotá, Secretaría de Salud de Bogotá, Bogotá, Colombia
| | - Hernan Vargas
- Grupo Laboratorio de Salud Pública de Bogotá, Secretaría de Salud de Bogotá, Bogotá, Colombia
| | - Charles Feldman
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Luis Felipe Reyes
- Universidad de la Sabana, Campus Puente del Común, KM 7.5 Autopista Norte de Bogotá, Chía, Colombia. .,Clínica Universidad de la Sabana, Chía, Colombia.
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Shuel M, Knox NC, Tsang RSW. Global population structure of Haemophilus influenzae serotype a (Hia) and emergence of invasive Hia disease: capsule switching or capsule replacement? Can J Microbiol 2021; 67:875-884. [PMID: 34379993 DOI: 10.1139/cjm-2021-0152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The population structure of Hia was examined by interrogation of the H. influenzae MLST website. There were 196 entries of Hia with 55 sequence types (STs) identified (as of September 3, 2020). BURST analysis clustered related STs into four complexes with ST-23, ST-4, ST-21 and ST-62 identified as their ancestral STs. The majority of Hia entries (73.4%) and STs (65.5%) were identified as clonal division I (ST-23 and the ST-4 complexes). Only 43 (21.9%) entries and 14 STs (25.5%) were identified as clonal division II (ST-62 and ST-21 complexes). Current data suggested most invasive Hia belonged to clonal division I and the ST-23 complex while most clonal division II Hia were respiratory isolates with the exception of ST-62 which was common among invasive Hia in the U.S. southwest. Comparison of the capsule bexABCD genes from clonal divisions I and II strains showed sequence diversity with variations following the pattern of clonal divisions. Evidence from the literature and the current study suggests recent emergence of invasive Hia might be related to capsule replacement subsequent to the implementation of the Hib conjugate vaccine and possibly exacerbated by other conjugate vaccines that may have altered the microbial flora of the human respiratory tract.
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Affiliation(s)
- Michelle Shuel
- National Microbiology Laboratory, 85072, 1015 Arlington Street, Winnipeg, Manitoba, Canada, R3E 3R2;
| | - Natalie C Knox
- Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington Street, Winnipeg, Manitoba, Canada, R3E 3R2.,University of Manitoba, 8664, Department of Medical Microbiology and Infectious Diseases, Room 543 - 745 Bannatyne Avenue, Winnipeg, Manitoba, Canada, R3E 0J9;
| | - Raymond S W Tsang
- CNS Infection Division and Vaccine Preventable Bacterial Diseases Division,, 1015 Arlington Street,, Winnipeg, Manitoba, Canada, R3E 3R2;
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van Beek LF, Surmann K, van den Berg van Saparoea HB, Houben D, Jong WSP, Hentschker C, Ederveen THA, Mitsi E, Ferreira DM, van Opzeeland F, van der Gaast-de Jongh CE, Joosten I, Völker U, Schmidt F, Luirink J, Diavatopoulos DA, de Jonge MI. Exploring metal availability in the natural niche of Streptococcus pneumoniae to discover potential vaccine antigens. Virulence 2021; 11:1310-1328. [PMID: 33017224 PMCID: PMC7550026 DOI: 10.1080/21505594.2020.1825908] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Nasopharyngeal colonization by Streptococcus pneumoniae is a prerequisite for pneumococcal transmission and disease. Current vaccines protect only against disease and colonization caused by a limited number of serotypes, consequently allowing serotype replacement and transmission. Therefore, the development of a broadly protective vaccine against colonization, transmission and disease is desired but requires a better understanding of pneumococcal adaptation to its natural niche. Hence, we measured the levels of free and protein-bound transition metals in human nasal fluid, to determine the effect of metal concentrations on the growth and proteome of S. pneumoniae. Pneumococci cultured in medium containing metal levels comparable to nasal fluid showed a highly distinct proteomic profile compared to standard culture conditions, including the increased abundance of nine conserved, putative surface-exposed proteins. AliA, an oligopeptide binding protein, was identified as the strongest protective antigen, demonstrated by the significantly reduced bacterial load in a murine colonization and a lethal mouse pneumonia model, highlighting its potential as vaccine antigen.
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Affiliation(s)
- Lucille F van Beek
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.,Radboud Center for Infectious Diseases , Nijmegen, The Netherlands
| | - Kristin Surmann
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald , Greifswald, Germany
| | | | | | | | - Christian Hentschker
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald , Greifswald, Germany
| | - Thomas H A Ederveen
- Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen, The Netherlands
| | - Elena Mitsi
- Liverpool School of Tropical medicine, Respiratory Infection Group , Liverpool, United Kingdom of Great Britain and Northern Ireland
| | - Daniela M Ferreira
- Liverpool School of Tropical medicine, Respiratory Infection Group , Liverpool, United Kingdom of Great Britain and Northern Ireland
| | - Fred van Opzeeland
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.,Radboud Center for Infectious Diseases , Nijmegen, The Netherlands
| | - Christa E van der Gaast-de Jongh
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.,Radboud Center for Infectious Diseases , Nijmegen, The Netherlands
| | - Irma Joosten
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands
| | - Uwe Völker
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald , Greifswald, Germany
| | - Frank Schmidt
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald , Greifswald, Germany.,Proteomics Core, Weill Cornell Medicine-Qatar , Doha, Qatar
| | - Joen Luirink
- Abera Bioscience AB , Solna, Sweden.,Department of Molecular Microbiology, Faculty of Science, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam , Amsterdam, The Netherlands
| | - Dimitri A Diavatopoulos
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.,Radboud Center for Infectious Diseases , Nijmegen, The Netherlands
| | - Marien I de Jonge
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.,Radboud Center for Infectious Diseases , Nijmegen, The Netherlands
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Narwortey DK, Owusu-Ofori A, Slotved HC, Donkor ES, Ansah PO, Welaga P, Agongo G, Oduro AR. Nasopharyngeal carriage of Streptococcus pneumoniae among healthy children in Kassena-Nankana districts of Northern Ghana. BMC Infect Dis 2021; 21:661. [PMID: 34233627 PMCID: PMC8265090 DOI: 10.1186/s12879-021-06302-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 05/17/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pneumococcal vaccine immunizations may be responsible for alterations in serotype epidemiology within a region. This study investigated the pneumococcal carriage prevalence and the impact of the 13-valent pneumococcal conjugate vaccine (PCV-13) on circulating serotypes among healthy children in Northern Ghana. METHODS This was a cross sectional study conducted in the Kassena-Nankana districts of Northern Ghana from November to December during the dry season of 2018. Nasopharyngeal swabs collected from 193 participants were cultured per standard microbiological protocols and pneumococcal isolates were serotyped using the latex agglutination technique and the capsular Quellung reaction test. We examined for any association between the demographic characteristics of study participants and pneumococcal carriage using chi-square test and logistic regression. RESULTS Of the 193 participants that were enrolled the mean age was 8.6 years and 54.4% were females. The carriage rate among the participants was 32.6% (63/193), and twenty different serotypes were identified. These included both vaccine serotypes (VT), 35% (7/20) and non-vaccine serotypes (NVT), 65% (13/20). The predominant serotypes (34 and 11A), both of which were NVT, accounted for a prevalence of 12.8%. PCV-13 covered only 35% of serotypes identified whiles 40% of serotypes are covered by PPV 23. CONCLUSION Post-vaccination carriage of S. pneumoniae is high and is dominated by non-vaccine serotypes. There is therefore a need for the conduct of invasive pneumococcal disease surveillance (IPD) to find out if the high non-vaccine serotype carriage translates to disease. And in addition, a review of the currently used PCV-13 vaccine in the country would be considered relevant.
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Affiliation(s)
- Deborah K. Narwortey
- Navrongo Health Research Centre, Ghana Health Services, Biomedical Department, P.O. Box 114, Navrongo, Ghana
- Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Alex Owusu-Ofori
- Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Hans-Christian Slotved
- Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
| | - Eric S. Donkor
- Department of Medical Microbiology, University of Ghana Medical School, Accra, Ghana
| | - Patrick O. Ansah
- Navrongo Health Research Centre, Ghana Health Services, Biomedical Department, P.O. Box 114, Navrongo, Ghana
| | - Paul Welaga
- Navrongo Health Research Centre, Ghana Health Services, Biomedical Department, P.O. Box 114, Navrongo, Ghana
| | - Godfred Agongo
- Navrongo Health Research Centre, Ghana Health Services, Biomedical Department, P.O. Box 114, Navrongo, Ghana
| | - Abraham R. Oduro
- Navrongo Health Research Centre, Ghana Health Services, Biomedical Department, P.O. Box 114, Navrongo, Ghana
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Streptococcus Pneumoniae-Associated Hemolytic Uremic Syndrome in the Era of Pneumococcal Vaccine. Pathogens 2021; 10:pathogens10060727. [PMID: 34207609 PMCID: PMC8227211 DOI: 10.3390/pathogens10060727] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/30/2021] [Accepted: 06/02/2021] [Indexed: 01/09/2023] Open
Abstract
Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS) is a serious complication of invasive pneumococcal disease that is associated with increased mortality in the acute phase and morbidity in the long term. Recently, Sp-HUS definition has undergone revision and cases are categorized as definite, probable, and possible, based on less invasive serological investigations that evaluate Thomsen-Friedenreich crypt antigen (T-antigen) activation. In comparison to the pre-vaccine era, Sp-HUS incidence seems to be decreasing after the introduction of 7-serotype valence and 13-serotype valence pneumococcal vaccines in 2000 and 2010, respectively. However, Sp-HUS cases continue to occur secondary to vaccine failure and emergence of non-vaccine/replacement serotypes. No single hypothesis elucidates the molecular basis for Sp-HUS occurrence, although pneumococcal neuraminidase production and formation of T-antigen antibody complexes on susceptible endothelial and red blood cells continues to remain the most acceptable explanation. Management of Sp-HUS patients remains supportive in nature and better outcomes are being reported secondary to earlier recognition, better diagnostic tools and improved medical care. Recently, the addition of eculizumab therapy in the management of Sp-HUS for control of dysregulated complement activity has demonstrated good outcomes, although randomized clinical trials are awaited. A sustained pneumococcal vaccination program and vigilance for replacement serotypes will be the key for persistent reduction in Sp-HUS cases worldwide.
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Kaur R, Pham M, Pichichero M. Serum antibody levels to pneumococcal polysaccharides 22F, 33F, 19A and 6A that correlate with protection from colonization and acute otitis media in children. Vaccine 2021; 39:3900-3906. [PMID: 34116872 DOI: 10.1016/j.vaccine.2021.05.089] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 04/16/2021] [Accepted: 05/23/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Serotypes 22F and 33F have been added to a new pneumococcal-conjugate vaccine (PCV-15) because of their prevalence in causing invasive pneumococcal diseases (IPD). METHOD We measured anti-polysaccharide 22F, 33F, 19A and 6A antibodies in children before and after pneumococcal colonization and acute otitis media (AOM) episodes caused by these specific-serotypes. A two-step method for construction of correlate of protection (COP) models included using a generalized estimating equation for the relationship between antibody level, age and colonization history followed by logistic-regression modelling that included colonization or AOM episodes as independent variables, and age adjusted antibody level as the predictor. RESULTS A vaccine-induced serum antibody level of 0.45 μg/ml for 22F, 0.51 μg/ml for 6A and 4.1 μg/ml for 19A correlated with prevention of pneumococcal colonization by respective serotypes (insufficient number of cases for 33F to find COP against colonization). Antibody levels of 0.25 μg/ml for 22F, 33F and 6A and 2 μg/ml for 19A correlated with prevention of AOM by the respective serotypes. CONCLUSIONS A COP threshold of anti-22F, 33F, 19A and 6A serum antibodies for NP colonization and AOM in young children can be derived using GEE and logistic regression modelling.
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Affiliation(s)
- Ravinder Kaur
- Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester, NY, United States.
| | - Minh Pham
- School of Mathematical Sciences, College of Science, Rochester Institute of Technology, Rochester, NY, United States
| | - Michael Pichichero
- Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester, NY, United States
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Park MA, Jenkins SM, Smith CY, Pyle RC, Sacco KA, Ryu E, Hagan JB, Joshi AY, Snyder MR, Abraham RS. Pneumococcal serotype-specific cut-offs based on antibody responses to pneumococcal polysaccharide vaccination in healthy adults. Vaccine 2021; 39:2850-2856. [PMID: 33896666 DOI: 10.1016/j.vaccine.2021.04.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 04/06/2021] [Accepted: 04/08/2021] [Indexed: 02/08/2023]
Abstract
Antibody responses to pneumococcal polysaccharide vaccination are frequently used as a diagnostic tool for humoral immunodeficiencies, part of the larger collection of inborn errors of immunity. Currently, arbitrary criteria, such as a serotype specific titer of >/= 1.3 µg/mL is most often used as a cut-off for interpretation of pneumococcal antibody responses. The magnitude of the antibody response to each of the 23 serotypes in Pneumovax®, and serotype-specific cut-offs in healthy pneumococcal vaccine-naïve adults has not been previously characterized. IgG antibody concentrations were measured prospectively for 23 pneumococcal serotypes pre and 4-6 weeks post-Pneumovax® vaccination in 100 healthy adults, using a multiplex bead-based assay. Antibodies to 19 of 23 serotypes were informative for distinguishing subjects who responded to vaccination, and the serotype threshold was determined to be 9 of 19 serotypes, which characterized an antibody response to pneumococcal vaccination. While this study may facilitate classification of IgG serotype-specific antibody responses post-pneumococcal vaccination in adult patients undergoing diagnostic immunological evaluation for antibody immunodeficiencies or other relevant contexts, additional studies in healthy children and S. pneumoniae protein-conjugate-vaccinated healthy adults will need to be undertaken in the future.
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Affiliation(s)
- Miguel A Park
- Division of Allergic Diseases, Department of Medicine, USA; Mayo Clinic, Rochester, MN, USA
| | - Sarah M Jenkins
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, USA; Mayo Clinic, Rochester, MN, USA
| | - Carin Y Smith
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, USA; Mayo Clinic, Rochester, MN, USA
| | - Regan C Pyle
- Division of Allergic Diseases, Department of Medicine, USA; Allergy, Asthma & Immunology of the Rockies, PC., Glenwood Springs, CO, USA
| | - Keith A Sacco
- Allergy & Immunology Program, National Institutes of Health, USA
| | - Euijung Ryu
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, USA; Mayo Clinic, Rochester, MN, USA
| | - John B Hagan
- Division of Allergic Diseases, Department of Medicine, USA; Mayo Clinic, Rochester, MN, USA
| | - Avni Y Joshi
- Division of Allergic Diseases, Department of Medicine, USA; Mayo Clinic, Rochester, MN, USA
| | - Melissa R Snyder
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Roshini S Abraham
- Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
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Genome-Wide Analysis of the Temporal Genetic Changes in Streptococcus pneumoniae Isolates of Genotype ST320 and Serotype 19A from South Korea. Microorganisms 2021; 9:microorganisms9040795. [PMID: 33920171 PMCID: PMC8069037 DOI: 10.3390/microorganisms9040795] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/08/2021] [Accepted: 04/08/2021] [Indexed: 12/05/2022] Open
Abstract
Since the introduction of the pneumococcal conjugate vaccine, an increase in the incidence of Streptococcus pneumoniae serotype 19A and sequence type 320 (19A-ST320) isolates have been observed worldwide including in South Korea. We conducted a genome-wide analysis to investigate the temporal genetic changes in 26 penicillin-non-susceptible 19A-ST320 pneumococcal isolates from a hospital in South Korea over a period of 17 years (1999; 2004 to 2015). Although the strains were isolated from a single hospital and showed the same genotype and serotype, a whole-genome sequencing (WGS) analysis revealed that the S. pneumoniae isolates showed more extensive genetic variations compared with a reference isolate obtained in 1999. A phylogenetic analysis based on single nucleotide polymorphisms (SNPs) showed that the pneumococcal isolates from South Korea were not grouped together into limited clusters among the 19A-ST320 isolates from several continents. It was predicted that recombination events occurred in 11 isolates; larger numbers of SNPs were found within recombination blocks compared with point mutations identified in five isolates. WGS data indicated that S. pneumoniae 19A-ST320 isolates might have been introduced into South Korea from various other countries. In addition, it was revealed that recombination may play a great role in the evolution of pneumococci even in very limited places and periods.
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Banerjee K, Motley MP, Diago-Navarro E, Fries BC. Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients. mSphere 2021; 6:e01335-20. [PMID: 33658281 PMCID: PMC8546725 DOI: 10.1128/msphere.01335-20] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 02/04/2021] [Indexed: 11/20/2022] Open
Abstract
Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR-Kp-infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR-Kp cultures. Isolate capsules were typed by wzi sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR-Kp CPS types (wzi29, wzi154, and wzi50). High IgG titers against wzi154 and wzi50 CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR-Kp and limited growth better than naive IgG and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from wzi50 and wzi154 patients promoted phagocytosis of nonconcordant CR-Kp serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with wzi50, wzi154, and wzi29 CR-Kp strains preopsonized with wzi50 patient-derived IgG exhibited lower lung CFU than controls. Depletion of wzi50 antibodies (Abs) reversed this effect in wzi50 and wzi154 infections, whereas wzi154 Ab depletion reduced poly-IgG efficacy against wzi29 CR-Kp We are the first to report cross-reactive properties of CPS-specific Abs from CR-Kp patients through both in vitro and in vivo models.IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is a rapidly emerging public health threat that can cause fatal infections in up to 50% of affected patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines is urgently needed. Capsular polysaccharides constitute important targets, as they are crucial for Klebsiella pneumoniae pathogenesis. Capsular polysaccharides are very diverse and, therefore, studying the host's capsule-type specific antibodies is crucial to develop effective anti-CPS immunotherapies. In this study, we are the first to characterize humoral responses in infected patients against carbapenem-resistant Klebsiella pneumoniae expressing different wzi capsule types. This study is the first to report the efficacy of cross-reactive properties of CPS-specific Abs in both in vitro and in vivo models.
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Affiliation(s)
- Kasturi Banerjee
- Department of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USA
- Veteran's Administration Medical Center, Northport, New York, USA
| | - Michael P Motley
- Department of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USA
- Department of Molecular Genetics and Immunology, Stony Brook University, Stony Brook, New York, USA
| | - Elizabeth Diago-Navarro
- Department of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USA
| | - Bettina C Fries
- Department of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USA
- Veteran's Administration Medical Center, Northport, New York, USA
- Department of Molecular Genetics and Immunology, Stony Brook University, Stony Brook, New York, USA
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Scott NR, Mann B, Tuomanen EI, Orihuela CJ. Multi-Valent Protein Hybrid Pneumococcal Vaccines: A Strategy for the Next Generation of Vaccines. Vaccines (Basel) 2021; 9:209. [PMID: 33801372 PMCID: PMC8002124 DOI: 10.3390/vaccines9030209] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/23/2021] [Accepted: 02/25/2021] [Indexed: 12/15/2022] Open
Abstract
Streptococcus pneumoniae (Spn) is a bacterial pathogen known to colonize the upper respiratory tract and cause serious opportunistic diseases such as pneumonia, bacteremia, sepsis and meningitis. As a consequence, millions of attributable deaths occur annually, especially among infants, the elderly and immunocompromised individuals. Although current vaccines, composed of purified pneumococcal polysaccharide in free form or conjugated to a protein carrier, are widely used and have been demonstrated to be effective in target groups, Spn has continued to colonize and cause life-threatening disease in susceptible populations. This lack of broad protection highlights the necessity of improving upon the current "gold standard" pneumococcal vaccines to increase protection both by decreasing colonization and reducing the incidence of sterile-site infections. Over the past century, most of the pneumococcal proteins that play an essential role in colonization and pathogenesis have been identified and characterized. Some of these proteins have the potential to serve as antigens in a multi-valent protein vaccine that confers capsule independent protection. This review seeks to summarize the benefits and limitations of the currently employed vaccine strategies, describes how leading candidate proteins contribute to pneumococcal disease development, and discusses the potential of these proteins as protective antigens-including as a hybrid construct.
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Affiliation(s)
- Ninecia R. Scott
- Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
| | - Beth Mann
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; (B.M.); (E.I.T.)
| | - Elaine I. Tuomanen
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; (B.M.); (E.I.T.)
| | - Carlos J. Orihuela
- Department of Microbiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
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Reslan L, Finianos M, Bitar I, Moumneh MB, Araj GF, Zaghlout A, Boutros C, Jisr T, Nabulsi M, Kara Yaccoub G, Hamze M, Osman M, Bou Raad E, Hrabak J, Matar GM, Dbaibo G. The Emergence of Invasive Streptococcus pneumoniae Serotype 24F in Lebanon: Complete Genome Sequencing Reveals High Virulence and Antimicrobial Resistance Characteristics. Front Microbiol 2021; 12:637813. [PMID: 33746930 PMCID: PMC7967862 DOI: 10.3389/fmicb.2021.637813] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 01/29/2021] [Indexed: 12/16/2022] Open
Abstract
Background Invasive pneumococcal disease (IPD) remains a global health problem. IPD incidence has significantly decreased by the use of pneumococcal conjugate vaccines (PCV). Nevertheless, non-PCV serotypes remain a matter of concern. Eight Streptococcus pneumoniae serotype 24F isolates, belonging to a non-PCV serotype, were detected through the Lebanese Inter-Hospital Pneumococcal Surveillance Program. The aim of the study is to characterize phenotypic and genomic features of the 24F isolates in Lebanon. Methods WGS using long reads sequencing (PacBio) was performed to produce complete circular genomes and to determine clonality, antimicrobial resistance and virulence determinants. Results The sequencing results yielded eight closed circular genomes. Three multilocus sequence typing (MLST) types were identified (ST11618, ST14184, ST15253). Both MLST and WGS analyses revealed that these isolates from Lebanon were genetically homogenous belonging to clonal complex CC230 and clustered closely with isolates originating from Canada, United States of America, United Kingdom and Iceland. Their penicillin binding protein profiles correlated with both β-lactam susceptibility patterns and MLST types. Moreover, the isolates harbored the macrolide and tetracycline resistance genes and showed a similar virulence gene profile. To our knowledge, this study represents the first report of complete phenotypic and genomic characterization of the emerging Streptococcus pneumoniae, serotype 24F, in the Middle East and North Africa region.
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Affiliation(s)
- Lina Reslan
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Marc Finianos
- Department of Microbiology, Faculty of Medicine and University Hospital in Plzen, Charles University, Plzen, Czechia
| | - Ibrahim Bitar
- Department of Microbiology, Faculty of Medicine and University Hospital in Plzen, Charles University, Plzen, Czechia
| | - Mohamad Bahij Moumneh
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - George F Araj
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon.,Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Alissar Zaghlout
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Celina Boutros
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon
| | - Tamima Jisr
- Department of Laboratory and Blood, Makassed General Hospital, Beirut, Lebanon
| | | | | | - Monzer Hamze
- Department of Microbiology, Nini Hospital, Tripoli, Lebanon
| | - Marwan Osman
- El-Youssef Hospital Center, Department of Clinical Laboratory, Halba, Lebanon
| | - Elie Bou Raad
- El-Youssef Hospital Center, Department of Clinical Laboratory, Halba, Lebanon
| | - Jaroslav Hrabak
- Department of Microbiology, Faculty of Medicine and University Hospital in Plzen, Charles University, Plzen, Czechia
| | - Ghassan M Matar
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon.,Department of Experimental Pathology, Immunology, and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Ghassan Dbaibo
- Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon.,Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
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40
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Palmu AA, De Wals P, Toropainen M, Ladhani SN, Deceuninck G, Knol MJ, Sanders EAM, Miller E. Similar impact and replacement disease after pneumococcal conjugate vaccine introduction in hospitalised children with invasive pneumococcal disease in Europe and North America. Vaccine 2021; 39:1551-1555. [PMID: 33610373 DOI: 10.1016/j.vaccine.2021.01.070] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 05/12/2020] [Accepted: 01/28/2021] [Indexed: 11/18/2022]
Abstract
High incidence of childhood invasive pneumococcal disease (IPD) in the US declined steeply after 7-valent pneumococcal conjugate vaccine (PCV7) introduction, outweighing reductions observed elsewhere. We re-analysed aggregate published data and compared pre- and post-PCV IPD-incidence in different countries to explore PCV impact on hospitalised and outpatient IPD separately. The proportion of hospitalised IPD cases was consistently high (>80%) in England&Wales, Finland, the Netherlands, and Quebec/Canada, but only 32% in the US before PCV introduction, increasing to 69% during the PCV era. In the US, a higher reduction in outpatient IPD incidence (94% in 2015 versus 1998-99) was observed compared to hospitalised IPD (79%); a 51% reduction in the non-PCV13-type IPD incidence among outpatient cases was estimated compared to a >2-fold increase for hospitalised cases. After stratification by hospitalization status, PCV programmes resulted in similar impact and serotype replacement in hospitalised IPD in US when compared to other countries.
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Affiliation(s)
- Arto A Palmu
- Department of Public Health Solutions, Finnish Institute for Health and Welfare, Tampere, Finland.
| | - Philippe De Wals
- Department of Social and Preventive Medicine, Laval University, Quebec City, Canada
| | - Maija Toropainen
- Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Shamez N Ladhani
- Department of Infectious Disease Epidemiology, Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, UK; Paediatric Infectious Diseases Research Group, St. George's University of London, London, UK
| | | | - Mirjam J Knol
- Center of Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - Elisabeth A M Sanders
- Center of Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht, the Netherlands
| | - Elizabeth Miller
- Department of Infectious Disease Epidemiology, Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, UK
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Ruiz García Y, Nieto Guevara J, Izurieta P, Vojtek I, Ortega-Barría E, Guzman-Holst A. CIRCULATING CLONAL COMPLEXES AND SEQUENCE TYPES OF STREPTOCOCCUS PNEUMONIAE SEROTYPE 19A WORLDWIDE: THE IMPORTANCE OF MULTIDRUG RESISTANCE: A SYSTEMATIC LITERATURE REVIEW. Expert Rev Vaccines 2021; 20:45-57. [PMID: 33507135 DOI: 10.1080/14760584.2021.1873136] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Streptococcus pneumoniae is a major cause of morbidity and mortality, especially amongst young children and the elderly. Childhood implementation of pneumococcal conjugate vaccines (PCVs) significantly reduced the incidence of invasive pneumococcal disease (IPD), while several nonvaccine serotypes remained substantial. Although there is evidence of the impact of higher-valent PCVs on serotype 19A, 19A IPD burden and antibiotic resistance remain a major concern post-vaccination. AREAS COVERED We performed a systematic literature review to analyze the frequency and clonal distribution of serotype 19A isolates in the pre- and post-PCV era worldwide providing a scientific background on the factors that influence multidrug resistance in pneumococcal isolates. EXPERT COMMENTARY Serotype 19A IPD incidence increased in all regions following the introduction of the 7-valent PCV. The higher-valent PCVs have reduced the rates of 19A IPD isolates, but several circulating strains with diverse antibiotic resistance prevailed. Heterogeneous clonal distribution in serotype 19A was observed within countries and regions, irrespective of higher-valent PCV used. An increase of 19A isolates from pre- to post-vaccination periods were associated with frequently occurring serotype switching events and with the prevalence of multidrug resistant strains. Rational antibiotic policies must be implemented to control the emergence of resistance.Plain Language SummaryWhat is the context?Streptococcus pneumoniae is a major cause of pneumococcal diseases especially amongst young children and the elderly. Vaccination with pneumococcal conjugate vaccines has significantly reduced the incidence of invasive pneumococcal disease worldwide. However, the invasive pneumococcal disease remains an important health problem due to the increase of nonvaccine serotypes. Serotype 19A is predominant in many countries worldwide. Factors contributing to its prevalence include serotype replacement, the emergence of clones with multidrug resistance due to antibiotic overuse, and potential bacteria adaptation in response to the vaccine.What is new?We performed a systematic literature review to 1) analyze the incidence and clonal distribution of serotype 19A isolates pre- and post-vaccination worldwide, and to collect data evaluating antimicrobial resistance patterns displayed by the clones of serotype 19A. We found that 1) clonal distribution in serotype 19A was heterogeneous within countries and regions, irrespective of the vaccine used; 2) the diversity of 19A isolates increased after vaccination. It was associated with frequent serotype switching events and with the prevalence of multidrug resistant strains.What is the impact?Implementation of policies to educate on sustainable antibiotic use and infectious prevention measures may help control the emergence of antibiotic resistance. High-quality active surveillance and future molecular epidemiology studies are needed to understand rapid genetic changes.
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Speck PG, Warner MS, Bihari S, Bersten AD, Mitchell JG, Tucci J, Gordon DL. Potential for bacteriophage therapy for Staphylococcus aureus pneumonia with influenza A coinfection. Future Microbiol 2021; 16:135-142. [PMID: 33538181 DOI: 10.2217/fmb-2020-0163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
The ability of influenza A virus to evolve, coupled with increasing antimicrobial resistance, could trigger an influenza pandemic with great morbidity and mortality. Much of the 1918 influenza pandemic mortality was likely due to bacterial coinfection, including Staphylococcus aureus pneumonia. S. aureus resists many antibiotics. The lack of new antibiotics suggests alternative antimicrobials, such as bacteriophages, are needed. Potential delivery routes for bacteriophage therapy (BT) include inhalation and intravenous injection. BT has recently been used successfully in compassionate access pulmonary infection cases. Phage lysins, enzymes that hydrolyze bacterial cell walls and which are bactericidal, are efficacious in animal pneumonia models. Clinical trials will be needed to determine whether BT can ameliorate disease in influenza and S. aureus coinfection.
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Affiliation(s)
- Peter G Speck
- Flinders University of South Australia, College of Science and Engineering, Bedford Park, SA, 5042, Australia
| | - Morgyn S Warner
- The Queen Elizabeth Hospital, Infectious Diseases Unit, Woodville, SA, 5011, Australia.,Microbiology & Infectious Diseases Directorate, SA Pathology, Adelaide, SA, 5000, Australia.,University of Adelaide, Faculty of Health & Medical Sciences, Adelaide, SA, 5006, Australia
| | - Shailesh Bihari
- Flinders Medical Centre, Intensive & Critical Care Unit, Bedford Park, SA, 5042, Australia.,Flinders University of South Australia, College of Medicine and Public Health, Bedford Park, SA, 5042, Australia
| | - Andrew D Bersten
- Flinders Medical Centre, Intensive & Critical Care Unit, Bedford Park, SA, 5042, Australia.,Flinders University of South Australia, College of Medicine and Public Health, Bedford Park, SA, 5042, Australia
| | - James G Mitchell
- Flinders University of South Australia, College of Science and Engineering, Bedford Park, SA, 5042, Australia
| | - Joseph Tucci
- Department of Pharmacy & Biomedical Science, LaTrobe University, La Trobe Institute for Molecular Science, Bendigo, Victoria, 3552, Australia
| | - David L Gordon
- Flinders University of South Australia, College of Medicine and Public Health, Bedford Park, SA, 5042, Australia.,Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, SA, 5042, Australia
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Dreyzin A, McCormick M, Zullo J, Shah SS, Kalpatthi R. Impact of PCV-13 vaccine on invasive pneumococcal disease in hospitalised children: A multi-institutional analysis. Acta Paediatr 2021; 110:624-630. [PMID: 32984994 DOI: 10.1111/apa.15594] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 06/07/2020] [Accepted: 09/22/2020] [Indexed: 11/29/2022]
Abstract
AIM We aimed to describe changes in invasive pneumococcal disease (IPD) hospitalisations after introduction of the pneumococcal conjugate vaccine (PCV13). METHODS This was a retrospective analysis of the Pediatric Health Information System (PHIS) database, including children with IPD pre-PCV13 (2004-2009) and post-PCV13 (2012-2017). Healthy children and those with chronic conditions were analysed separately. The primary outcome was IPD incidence. Secondary outcomes included length of stay, intensive care unit (ICU) admission, mechanical ventilation and mortality. RESULTS 9160 hospitalisations for IPD were included. The IPD rate per 100 000 discharges was 180 pre-PVC13 and 150 post-PCV13 [17% decrease (P = 0.085)]. The observed IPD rate in 2017 was 45.5% lower than the rate predicted by the pre-PCV13 trend (95% CI: 44%-46%). While a significant decrease in IPD (32%, P = 0.026) was observed among healthy children, there was no change in those with chronic conditions (9%, P = 0.24). In the post-PCV13 period, more IPD patients had chronic conditions, ICU admissions and longer ICU stays. CONCLUSION Although there was no overall reduction in IPD after PCV13, we observed a significant decrease in IPD among healthy patients. Further research is needed to elucidate microbiology or other factors contributing to persistent IPD hospitalisations.
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Affiliation(s)
- Alexandra Dreyzin
- Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh PA USA
| | - Meghan McCormick
- Division of Hematology/Oncology UPMC Children’s Hospital of Pittsburgh Pittsburgh PA USA
| | - James Zullo
- UPMC Children’s Hospital of Pittsburgh Pittsburgh PA USA
| | - Samir S. Shah
- Cincinnati Children’s Hospital Medical Center Pittsburgh PA USA
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Madhi SA, Knoll MD. An affordable pneumococcal conjugate vaccine after 20 years. THE LANCET. INFECTIOUS DISEASES 2021; 21:751-753. [PMID: 33516294 DOI: 10.1016/s1473-3099(21)00002-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 01/04/2021] [Indexed: 11/24/2022]
Affiliation(s)
- Shabir A Madhi
- South African Medical Research Council Vaccines and Infectious Diseases Analytical Research Unit and Department of Science/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Science, Johannesburg 2013, South Africa.
| | - Maria Deloria Knoll
- Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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del Rosal T, Caminoa MB, González-Guerrero A, Falces-Romero I, Romero-Gómez MP, Baquero-Artigao F, Sainz T, Méndez-Echevarría A, Escosa-García L, Aracil FJ, Calvo C. Outcome of Severe Bacterial Pneumonia in the Era of Pneumococcal Vaccination. Front Pediatr 2020; 8:576519. [PMID: 33384973 PMCID: PMC7769833 DOI: 10.3389/fped.2020.576519] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 11/27/2020] [Indexed: 11/13/2022] Open
Abstract
Introduction: After the introduction of pneumococcal conjugate vaccines, community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae has decreased whereas Staphylococcus aureus and Streptococcus pyogenes could be increasing. These bacteria have been associated with high rates of complications. Aims: (1) To describe the characteristics of pediatric bacterial CAP requiring hospitalization. (2) To compare outcomes according to causative microorganisms. (3) To analyze changes in bacterial CAP rate and etiology over time. Patients and Methods: Retrospective single-center study of inpatients aged 1 month-16 years with culture-confirmed bacterial CAP in 2010-2018 in Madrid, Spain. Results: We included 64 cases (42 S. pneumoniae, 13 S. pyogenes and 9 S. aureus). Culture-confirmed CAP represented 1.48-2.33/1,000 all-cause pediatric hospital admissions, and its rate did not vary over time. However, there was a significant decrease in pneumococcal CAP in the last 3 years of the study (78% of CAP in 2010-2015 vs. 48% in 2016-18, p = 0.017). Median hospital stay was 10.5 days (interquartile range 5-19.5), 38 patients (59%) developed complications and 28 (44%) were admitted to the intensive care unit. Outcomes were similar among children with S. pneumoniae and S. aureus CAP, whereas S. pyogenes was associated with a higher risk for complications (OR 8 [95%CI 1.1-57.2]) and ICU admission (OR 7.1 [95%CI 1.7-29.1]) compared with pneumococcal CAP. Conclusion: In a setting with high PCV coverage, culture-confirmed bacterial CAP did not decrease over time and there was a relative increase of S. pyogenes and S. aureus. Children with CAP caused by S. pyogenes were more likely to develop complications.
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Affiliation(s)
- Teresa del Rosal
- Department of Pediatric Infectious Diseases, Hospital Universitario La Paz and IdiPAZ Research Institute, Madrid, Spain
| | | | - Alba González-Guerrero
- Department of Pediatric Infectious Diseases, Hospital Universitario La Paz and IdiPAZ Research Institute, Madrid, Spain
| | - Iker Falces-Romero
- Department of Microbiology, Hospital Universitario La Paz, Madrid, Spain
| | | | - Fernando Baquero-Artigao
- Department of Pediatric Infectious Diseases, Hospital Universitario La Paz and IdiPAZ Research Institute, Madrid, Spain
| | - Talía Sainz
- Department of Pediatric Infectious Diseases, Hospital Universitario La Paz and IdiPAZ Research Institute, Madrid, Spain
- Red de Investigación Traslacional en Infectología Pediátrica, Madrid, Spain
| | - Ana Méndez-Echevarría
- Department of Pediatric Infectious Diseases, Hospital Universitario La Paz and IdiPAZ Research Institute, Madrid, Spain
| | - Luis Escosa-García
- Department of Pediatric Infectious Diseases, Hospital Universitario La Paz and IdiPAZ Research Institute, Madrid, Spain
| | - Francisco Javier Aracil
- Department of Pediatric Infectious Diseases, Hospital Universitario La Paz and IdiPAZ Research Institute, Madrid, Spain
| | - Cristina Calvo
- Department of Pediatric Infectious Diseases, Hospital Universitario La Paz and IdiPAZ Research Institute, Madrid, Spain
- Red de Investigación Traslacional en Infectología Pediátrica, Madrid, Spain
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Hu T, Weiss T, Owusu-Edusei K, Petigara T. Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in children in the United States. J Med Econ 2020; 23:1653-1660. [PMID: 33084447 DOI: 10.1080/13696998.2020.1840216] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIMS V114 is an investigational 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 Streptococcus pneumoniae serotypes in 13-valent PCV (PCV13) plus two additional serotypes. This study quantified the health and economic burden of invasive pneumococcal disease (IPD) and acute otitis media (AOM) caused by V114 types among children in the United States. MATERIALS AND METHODS A Markov model estimated the number of V114-type IPD and AOM cases and costs in a hypothetical, unvaccinated US birth cohort over 20 years. Three time periods were analyzed using time-specific epidemiological data to determine the number of IPD and AOM cases associated with all 15 serotypes in V114. The time periods were: (1) pre-PCV7 (1999); (2) pre-PCV13 (2009); (3) post-PCV13 (2017). Costs were estimated from a societal perspective (2018 US dollars) and discounted at 3%. RESULTS The model estimated 18,983 IPD cases and 5.4 million AOM cases associated with V114 serotypes pre-PCV7, 4,697 IPD cases and 3.0 million AOM cases pre-PCV13, and 948 IPD cases and 0.2 million AOM cases post-PCV13. Total discounted costs associated with V114 serotypes were $1.7 billion pre-PCV7, $730 million pre-PCV13, and $75 million US dollars post-PCV13. LIMITATIONS Post-meningitis sequelae, cases of non-bacteremic pneumonia, and direct non-medical costs were not included. CONCLUSIONS IPD and AOM cases and costs were estimated in a hypothetical US birth cohort followed for 20 years at three time periods. In all three periods, the serotypes targeted by V114 contributed to significant morbidity and costs. New pediatric pneumococcal vaccines must continue to retain serotypes in licensed vaccines to maintain disease reduction while extending coverage to non-vaccine serotypes.
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Affiliation(s)
- Tianyan Hu
- Center for Observational and Real-world Evidence, Merck & Co., Inc., Kenilworth, NJ, USA
| | - Thomas Weiss
- Center for Observational and Real-world Evidence, Merck & Co., Inc., Kenilworth, NJ, USA
| | - Kwame Owusu-Edusei
- Center for Observational and Real-world Evidence, Merck & Co., Inc., Kenilworth, NJ, USA
| | - Tanaz Petigara
- Center for Observational and Real-world Evidence, Merck & Co., Inc., Kenilworth, NJ, USA
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Hink RK, Adam HJ, Golden AR, Baxter M, Martin I, Nichol KA, Demczuk W, Mulvey MR, Karlowsky JA, Zhanel GG. Comparison of PCV-10 and PCV-13 vaccine coverage for invasive pneumococcal isolates obtained across Canadian geographic regions, SAVE 2011 to 2017. Diagn Microbiol Infect Dis 2020; 99:115282. [PMID: 33341491 DOI: 10.1016/j.diagmicrobio.2020.115282] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 11/19/2020] [Accepted: 11/21/2020] [Indexed: 01/08/2023]
Abstract
To assess the coverage of invasive Streptococcus pneumoniae by pneumococcal conjugate vaccines (PCV)-10 and PCV-13 across Canada. In total, 9166 invasive S. pneumoniae isolates were collected as part of the SAVE 2011 to 2017 study. Serotyping was performed by the Quellung reaction and antimicrobial susceptibility testing was performed using CLSI methods. The proportion of both PCV-10 and PCV-13 serotypes decreased significantly (P < 0.0001) from 2011 (26.7% and 48.0%, respectively) to 2017 (11.2% and 26.2%). For central, western, and eastern regions of Canada, PCV-13 provided significantly greater (P < 0.0001) coverage at 33.7% (2060/6110), 23.0% (456/1985), and 36.3% (389/1071), respectively, compared to PCV-10 at 15.4% (939/6110), 10.1% (201/1985), and 15.8% (169/1071) coverage. PCV-13 provided significantly greater coverage (53.3%, 282/529) of multidrug-resistant (MDR) isolates (resistant to ≥3 antimicrobial classes) than PCV-10 (14.6%, 77/529, P < 0.0001). PCV-13 provided significantly greater coverage of invasive S. pneumoniae serotypes, as well as coverage of MDR isolates, than PCV-10.
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Affiliation(s)
- Rachel K Hink
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada
| | - Heather J Adam
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada; Clinical Microbiology, Diagnostic Services, Shared Health, Health Sciences Centre, Winnipeg, Manitoba, R3A 1R9, Canada
| | - Alyssa R Golden
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada
| | - Melanie Baxter
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada
| | - Irene Martin
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2, Canada
| | - Kimberly A Nichol
- Clinical Microbiology, Diagnostic Services, Shared Health, Health Sciences Centre, Winnipeg, Manitoba, R3A 1R9, Canada
| | - Walter Demczuk
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2, Canada
| | - Michael R Mulvey
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2, Canada
| | - James A Karlowsky
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada; Clinical Microbiology, Diagnostic Services, Shared Health, Health Sciences Centre, Winnipeg, Manitoba, R3A 1R9, Canada
| | - George G Zhanel
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada.
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Peckeu L, van der Ende A, de Melker HE, Sanders EAM, Knol MJ. Impact and effectiveness of the 10-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among children under 5 years of age in the Netherlands. Vaccine 2020; 39:431-437. [PMID: 33243632 DOI: 10.1016/j.vaccine.2020.11.018] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 11/03/2020] [Accepted: 11/05/2020] [Indexed: 11/17/2022]
Abstract
BACKGROUND In 2011, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 10-valent vaccine (PCV10) in the Netherlands. We report on impact and effectiveness against invasive pneumococcal disease (IPD) in children aged under 5 years by switching from PCV7 to PCV10. METHOD We included IPD cases between 2004 and 2019 in children aged < 5 years reported via the national surveillance system. To assess the impact of the PCV10 vaccination program we compared IPD incidence 6-8 years after PCV10 introduction (2017-2019) to the two years just before the switch to PCV10 (2009-2011). We estimated vaccine effectiveness (VE) using the indirect cohort method, comparing vaccination status (at least two vaccine doses) in IPD-cases caused by PCV10 serotypes (cases) to non-PCV10 IPD cases (controls), in children eligible for PCV10. RESULTS The overall incidence decreased from 8.7 (n = 162) in 2009-2011 to 7.3 per 100.000 (n = 127) in 2017-2019 (Incidence rate ratio (IRR) 0.83, 95%CI: 0.66; 1.05). IPD caused by the additional serotypes included in PCV10 declined by 93% (IRR 0.07, 95%CI: 0.02; 0.23). Incidence of non-PCV10 IPD showed a non-significant increase (IRR 1.25, 95%CI: 0.96; 1.63). Among 231 IPD-cases eligible for PCV10, the overall VE was 91% (95%CI: 67; 97) and did not differ by sex or age at diagnosis. Effectiveness against non-PCV10 serotype 19A IPD was non-significant with an estimate of 28% (95%CI:-179; 81). CONCLUSION PCV10 is highly effective in protecting against IPD in Dutch children under 5 years with limited serotype replacement after switching from PCV7 to PCV10. We found no evidence for significant cross-protection of PCV10 against 19A serotype IPD.
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Affiliation(s)
- L Peckeu
- European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - A van der Ende
- Amsterdam UMC, University of Amsterdam, Medical Microbiology and Infection Prevention and the Netherlands Reference Laboratory of Bacterial Meningitis, Amsterdam, the Netherlands
| | - H E de Melker
- National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - E A M Sanders
- National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - M J Knol
- National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
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49
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Pelton SI, Bornheimer R, Doroff R, Shea KM, Sato R, Weycker D. Decline in Pneumococcal Disease Attenuated in Older Adults and Those With Comorbidities Following Universal Childhood PCV13 Immunization. Clin Infect Dis 2020; 68:1831-1838. [PMID: 30239637 PMCID: PMC6522679 DOI: 10.1093/cid/ciy800] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 09/14/2018] [Indexed: 11/13/2022] Open
Abstract
Background Following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, epidemiology of pneumococcal disease shifted such that disease incidence in the elderly exceeded that in children. We evaluated the impact of replacing PCV7 with PCV13 on disease burden in adults and identified age/risk-specific subgroups with the highest remaining disease burden. Methods A retrospective design and data from two US healthcare claims repositories were used. Study population included adults aged ≥18 years and was stratified by age (18–49, 50–64, 65–74, ≥75) and risk profile (healthy, at-risk, high-risk). Rate ratios comparing invasive pneumococcal disease (IPD), all-cause hospitalized pneumonia (ACHP), and pneumococcal pneumonia requiring hospitalization among at-risk and high-risk adults vs healthy counterparts were estimated for 2007–2010 (pre-PCV13), 2011–2012 (peri-PCV13), and 2013–2015 (post-PCV13). Results Across study periods, IPD and ACHP rates increased with age (2–27 times higher in persons ≥75 vs 18–49) and comorbidity (4–20 times higher in high-risk vs healthy). From pre- to post-PCV13 period, IPD rates declined 5%–48% and ACHP rates declined 4%–19% across age and risk groups (ACHP did not decline in persons ≥75). Decline in IPD and ACHP was attenuated among older adults and those with comorbidities. Accordingly, rate ratios among at-risk and high-risk persons (vs healthy counterparts) increased during the peri- and post-PCV13 periods compared with the pre-PCV13 period. Conclusions The switch to PCV13 was associated with large declines in pneumococcal disease among US adults. However, the decline was attenuated with increasing age (and, for ACHP, was absent in persons ≥75) and in those with comorbidities.
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Affiliation(s)
- Stephen I Pelton
- Boston University Schools of Medicine and Public Health, Massachusetts.,Boston Medical Center, Massachusetts
| | | | | | - Kimberly M Shea
- Boston University Schools of Medicine and Public Health, Massachusetts
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50
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Voß F, van Beek LF, Schwudke D, Ederveen THA, van Opzeeland FJ, Thalheim D, Werner S, de Jonge MI, Hammerschmidt S. Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection. Vaccines (Basel) 2020; 8:vaccines8020310. [PMID: 32560374 PMCID: PMC7350230 DOI: 10.3390/vaccines8020310] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/04/2020] [Accepted: 06/11/2020] [Indexed: 12/20/2022] Open
Abstract
Streptococcus pneumoniae infections lead to high morbidity and mortality rates worldwide. Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but have a limited range of protection, which encourages the development of a broadly protective protein-based alternative. We and others have shown that immunization with pneumococcal lipoproteins that lack the lipid anchor protects against colonization. Since immunity against S. pneumoniae is mediated through Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects of a lipid modification on the induced immune responses in either intranasally or subcutaneously vaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrA strongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhanced antibody concentrations and different induction kinetics. The induced humoral immune response was modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-type immunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderate but consistent reduction of pneumococcal colonization as compared to the non-lipidated proteins, indicating that protein lipidation can improve the protective capacity of the coupled antigen. Thus, protein lipidation represents a promising approach for the development of a serotype-independent pneumococcal vaccine.
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Affiliation(s)
- Franziska Voß
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, Germany; (F.V.); (D.T.); (S.W.)
| | - Lucille F. van Beek
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands; (L.F.v.B.); (F.J.v.O.); (M.I.d.J.)
- Radboud Center for Infectious Diseases, Radboudumc, 6525 GA Nijmegen, The Netherlands
| | - Dominik Schwudke
- Division of Bioanalytical Chemistry, Priority Area Infection, Research Center Borstel, Leibniz Center for Medicine and Bioscience, 23845 Borstel, Germany;
- German Center for Infection Research (DZIF), 38124 Braunschweig, Germany
- Airway Research Center North Member of the German Center for Lung Research (DZL), 22927 Großhansdorf, Germany
| | - Thomas H. A. Ederveen
- Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;
| | - Fred J. van Opzeeland
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands; (L.F.v.B.); (F.J.v.O.); (M.I.d.J.)
- Radboud Center for Infectious Diseases, Radboudumc, 6525 GA Nijmegen, The Netherlands
| | - Daniela Thalheim
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, Germany; (F.V.); (D.T.); (S.W.)
| | - Sidney Werner
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, Germany; (F.V.); (D.T.); (S.W.)
| | - Marien I. de Jonge
- Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands; (L.F.v.B.); (F.J.v.O.); (M.I.d.J.)
- Radboud Center for Infectious Diseases, Radboudumc, 6525 GA Nijmegen, The Netherlands
| | - Sven Hammerschmidt
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, 17489 Greifswald, Germany; (F.V.); (D.T.); (S.W.)
- Correspondence: ; Tel.: +49-383-4420-5700; Fax: +49-3834-4205-709
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