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Meyers E, De Rop L, Deschepper E, Duysburgh E, De Burghgraeve T, Van Ngoc P, Digregorio M, Coen A, De Clercq N, Wallaert S, Buret L, Coenen S, De Sutter A, Scholtes B, Verbakel JY, Cools P, Heytens S. SARS-CoV-2 seroreversion and all-cause mortality in nursing home residents and staff post-primary course vaccination in Belgium between February and December 2021. Vaccine 2025; 51:126865. [PMID: 39983537 DOI: 10.1016/j.vaccine.2025.126865] [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: 02/22/2024] [Revised: 02/05/2025] [Accepted: 02/06/2025] [Indexed: 02/23/2025]
Abstract
BACKGROUND During COVID-19 vaccine implementation, information on the persistence of antibody response and impact on mortality in nursing home residents was limited, as they were underrepresented in vaccine clinical trials and real-world data was lacking. OBJECTIVES (1) Measure the persistence of the SARS-CoV-2 antibody response and predictors for seroreversion after primary course COVID-19 vaccination in nursing home residents compared to staff and (2) assess all-cause mortality and predictors in nursing home residents after primary COVID-19 vaccination. METHODS Seroprevalence and mortality data were collected within a national serosurveillance study in 1640 residents and 1368 staff from 69 nursing homes proportionally spread across Belgium between February and December 2021. To assess the persistence of the antibody response, parametric exponential survival models with interval censoring were fitted, reported with the percentage of seroreverters 120 and 140 days post-primary course vaccination. Furthermore, all-cause mortality rate was calculated and COVID-19 mortality was descriptively reported. Predictors of seroreversion and all-cause mortality were estimated using Cox proportional hazards model. RESULTS Nursing home residents were 47 % more likely to serorevert in the 10 months after COVID-19 vaccination than staff. Infection naïvety, older age and high resident care dependency level were found as predictors for seroreversion. The all-cause mortality rate in vaccinated residents over 10 months was 14 % (95 % CI 13-16 %) (n = 229). In 2 % of cases, COVID-19 infection was the reported cause of death. Older age, being male, having severe renal, lung, or cardiac disease, or active cancer, and high care dependency level were identified as predictors for all-cause mortality, irrespective of history of SARS-CoV-2 or breakthrough infection. CONCLUSION/PRACTICAL IMPLICATION Future COVID-19 vaccination strategies should prioritize (infection naïve) nursing home residents, as they fail to mount a durable antibody response after primary course vaccination. Nevertheless, COVID-19 mortality remained low, representing only 2 % of the all-cause mortality rate. This study was registered on ClinicalTrials.gov (NCT04738695).
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Affiliation(s)
- Eline Meyers
- Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Liselore De Rop
- LUHTAR, Leuven Unit for HTA Research, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium
| | - Ellen Deschepper
- Biostatistics Unit, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Els Duysburgh
- Department of Epidemiology and Public Health, Sciensano, 1000 Brussels, Belgium
| | - Tine De Burghgraeve
- LUHTAR, Leuven Unit for HTA Research, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium
| | - Pauline Van Ngoc
- Research Unit of Primary Care and Health, Department of General Medicine, Faculty of Medicine, University of Liège, 4000 Liège, Belgium
| | - Marina Digregorio
- Research Unit of Primary Care and Health, Department of General Medicine, Faculty of Medicine, University of Liège, 4000 Liège, Belgium
| | - Anja Coen
- Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Nele De Clercq
- Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Steven Wallaert
- Biostatistics Unit, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Laëtitia Buret
- Research Unit of Primary Care and Health, Department of General Medicine, Faculty of Medicine, University of Liège, 4000 Liège, Belgium
| | - Samuel Coenen
- Department of Family Medicine & Population Health, Faculty of Medicine and Health Sciences, University of Antwerp, 2000 Antwerp, Belgium
| | - An De Sutter
- Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Beatrice Scholtes
- Research Unit of Primary Care and Health, Department of General Medicine, Faculty of Medicine, University of Liège, 4000 Liège, Belgium
| | - Jan Y Verbakel
- LUHTAR, Leuven Unit for HTA Research, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium; NIHR Community Healthcare Medtech and IVD cooperative, Nuffield Department of Primary Care Health Sciences, University of Oxford, OX1 2JD Oxford, United Kingdom
| | - Piet Cools
- Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Stefan Heytens
- Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
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Abul Y, Nugent C, Vishnepolskiy I, Wallace T, Dickerson E, Holland L, Esparza I, Winkis M, Wali KT, Chan PA, Baier RR, Recker A, Kaczynski M, Kamojjala S, Pralea A, Rice H, Osias O, Oyebanji OA, Olagunju O, Cao Y, Li CJ, Roederer A, Pfeifer WM, Bosch J, King CL, Nanda A, McNicoll L, Mujahid N, Raza S, Tyagi R, Wilson BM, White EM, Canaday DH, Gravenstein S, Balazs AB. Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents. GeroScience 2025; 47:1887-1896. [PMID: 39395130 PMCID: PMC11978566 DOI: 10.1007/s11357-024-01346-2] [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: 07/03/2024] [Accepted: 09/05/2024] [Indexed: 10/14/2024] Open
Abstract
SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs) but emerging variants and waning immunity challenge vaccine effectiveness. This study assesses the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Participants were subset of a longitudinal study of consented NHRs and Healthcare workers (HCWs) who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine post-FDA approval in Fall 2023. NHRs were categorized by whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). After XBB.1.5 vaccination, a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers was observed:17.3 (95% confidence interval [CI] 9.3, 32.4) and NHRs with interval infection and 11.3 (95% CI 5, 25.4) in those without and 13.6 (95% CI 8.4,22) in HCWs. For JN.1-specific titers, GMFRs were 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) in NHRs with and without interval infection, and 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher titers across all analyzed strains analyzed. The XBB.1.5 vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs with more pronounced in those previously infected with SARS-CoV-2 since bivalent vaccination.
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Affiliation(s)
- Yasin Abul
- Center On Innovation in Long-Term Services & Supports, Providence Veterans Administration Medical Center, Providence, RI, USA.
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA.
- Case Western Reserve University School of Medicine, Cleveland, OH, USA.
- Brown University School of Public Health, Providence, RI, USA.
| | - Clare Nugent
- Division of Geriatrics and Palliative Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Igor Vishnepolskiy
- Center On Innovation in Long-Term Services & Supports, Providence Veterans Administration Medical Center, Providence, RI, USA
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Tiffany Wallace
- Division of Geriatrics and Palliative Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Evan Dickerson
- Division of Geriatrics and Palliative Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Laurel Holland
- Division of Geriatrics and Palliative Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Iva Esparza
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Mandi Winkis
- Division of Geriatrics and Palliative Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Kazi Tanvee Wali
- Division of Geriatrics and Palliative Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Philip A Chan
- Division of Infectious Diseases, Warren Alpert Medical School of Brown University, Providence, RI, USA
- Brown University School of Public Health, Providence, RI, USA
| | - Rosa R Baier
- Brown University School of Public Health, Providence, RI, USA
| | - Amy Recker
- Brown University School of Public Health, Providence, RI, USA
| | - Matthew Kaczynski
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Shreya Kamojjala
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Alexander Pralea
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Hailee Rice
- Division of Geriatrics and Palliative Medicine, Rhode Island Hospital, Providence, RI, USA
| | - Olubunmi Osias
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | | | - Olajide Olagunju
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Yi Cao
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
| | - Chia Jung Li
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
| | - Alex Roederer
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
| | | | - Jürgen Bosch
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | | | - Aman Nanda
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Lynn McNicoll
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Nadia Mujahid
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Sakeena Raza
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Rohit Tyagi
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
| | - Brigid M Wilson
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Geriatric Research, Education and Clinical Center, VA Northeast Ohio Healthcare System, Cleveland, VA, USA
| | | | - David H Canaday
- Case Western Reserve University School of Medicine, Cleveland, OH, USA.
- Geriatric Research, Education and Clinical Center, VA Northeast Ohio Healthcare System, Cleveland, VA, USA.
| | - Stefan Gravenstein
- Center On Innovation in Long-Term Services & Supports, Providence Veterans Administration Medical Center, Providence, RI, USA
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
- Brown University School of Public Health, Providence, RI, USA
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Hofstee MI, Kaczorowska J, Postema A, Zomer E, van Waalwijk M, Jonathans G, de Rond LG, Smits G, van den Hoogen LL, den Hartog G, Buisman AM. High SARS-CoV-2 antibody levels after three consecutive BNT162b2 booster vaccine doses in nursing home residents. Immun Ageing 2025; 22:1. [PMID: 39748353 PMCID: PMC11694371 DOI: 10.1186/s12979-024-00495-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 12/23/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND As older age and having certain comorbidities can influence humoral responses to vaccination, we studied antibody responses after the COVID-19 booster campaigns in nursing home (NH) residents. METHODS In a two year longitudinal study with Dutch NH residents (n = 107), aged 50 years and over, we monitored antibody responses in serum prior to and after vaccination with a third, fourth BNT162b2 (wild-type; WT), and a BNT162b2 bivalent (WT/OMI BA.1) fifth vaccine. Data on vaccinations, infections, comorbidities, and, for some participants, clinical symptoms after infection were obtained with questionnaires. Data were compared to antibody responses of BNT162b2-vaccinated, healthier community-dwelling older adults (n = 32) from the general population. RESULTS The booster vaccinations substantially increased anti-WT and anti-Omicron SARS-CoV-2 Spike S1 (S1) and Spike protein receptor binding domain (RBD)-antibody concentrations of NH residents. This resulted in comparable antibody levels between NH residents and healthier community-dwelling older adults and between infection-naïve and infected NH residents, and in a decline in treatment duration and clinical symptom severity in SARS-CoV-2-infected NH residents. Between one and twelve months after the bivalent fifth dose, anti-Omicron BA.1 antibody levels of the NH residents waned faster than those against the WT strain. CONCLUSIONS The booster vaccinations upheld humoral responses of NH residents to WT and Omicron SARS-CoV-2. This, in addition to the less virulent circulating strains, decreased symptom severity and treatment durations for SARS-CoV-2-infected NH residents. Boosting this vulnerable group should, therefore, be continued to prevent waning of humoral immunity and achieve sufficient protection especially against newly emerging variants of concern.
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Affiliation(s)
- Marloes I Hofstee
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, 9, 3721MA, The Netherlands
| | - Joanna Kaczorowska
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, 9, 3721MA, The Netherlands
| | - Abigail Postema
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, 9, 3721MA, The Netherlands
| | | | | | - Gustaaf Jonathans
- Amstelring, Location Nursing Home Bornholm, Bornholm 50, Hoofddorp, The Netherlands
| | - Lia Gh de Rond
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, 9, 3721MA, The Netherlands
| | - Gaby Smits
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, 9, 3721MA, The Netherlands
| | - Lotus L van den Hoogen
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, 9, 3721MA, The Netherlands
| | - Gerco den Hartog
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, 9, 3721MA, The Netherlands
- Laboratory of Medical Immunology, Radboudumc, Nijmegen, The Netherlands
| | - Anne-Marie Buisman
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, 9, 3721MA, The Netherlands.
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Roederer AL, Cao Y, St Denis K, Sheehan ML, Li CJ, Lam EC, Gregory DJ, Poznansky MC, Iafrate AJ, Canaday DH, Gravenstein S, Garcia-Beltran WF, Balazs AB. Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity. Cell Rep Med 2024; 5:101850. [PMID: 39657661 PMCID: PMC11722104 DOI: 10.1016/j.xcrm.2024.101850] [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: 09/13/2024] [Revised: 10/24/2024] [Accepted: 11/12/2024] [Indexed: 12/12/2024]
Abstract
With the onset of the COVID-19 pandemic 4 years ago, viral sequencing continues to document numerous individual mutations in the viral spike protein across many variants. To determine the ability of vaccine-mediated humoral immunity to combat continued SARS-CoV-2 evolution, we construct a comprehensive panel of pseudoviruses harboring each individual mutation spanning 4 years of the pandemic to understand the fitness cost and resistance benefits of each. These efforts identify numerous mutations that escape from vaccine-induced humoral immunity. Across 50 variants and 131 mutants we construct, we observe progressive loss of neutralization across variants, irrespective of vaccine doses, as well as increasing infectivity and ACE2 binding. Importantly, the recent XBB.1.5 booster significantly increases titers against most variants but not JN.1, KP.2, or KP.3. These findings demonstrate that variants continue to evade updated mRNA vaccines, highlighting the need for different approaches to control SARS-CoV-2 transmission.
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Affiliation(s)
- Alex L Roederer
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
| | - Yi Cao
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
| | - Kerri St Denis
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
| | - Maegan L Sheehan
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
| | - Chia Jung Li
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
| | - Evan C Lam
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
| | - David J Gregory
- Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA 02129, USA; Pediatric Infectious Disease, Massachusetts General Hospital for Children, Boston, MA 02114, USA
| | - Mark C Poznansky
- Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA 02129, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
| | - A John Iafrate
- Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - David H Canaday
- Case Western Reserve University School of Medicine, Cleveland, OH, USA; Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA
| | - Stefan Gravenstein
- Center of Innovation in Long-Term Services and Supports, Veterans Administration Medical Center, Providence, RI, USA; Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI, USA; Brown University School of Public Health Center for Gerontology and Healthcare Research, Providence, RI, USA
| | - Wilfredo F Garcia-Beltran
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA
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Shrestha LB, Tungatt K, Aggarwal A, Stubis A, Fewings NL, Fichter C, Akerman A, Rodrigo C, Tedla N, Lee S, Lloyd AR, Brilot F, Britton WJ, Kelleher A, Caterson ID, Douglas MW, Rockett R, Tangye SG, Triccas JA, Turville SG, Sandgren KJ, Bull RA, Cunningham AL. Bivalent Omicron BA.1 vaccine booster increases memory B cell breadth and neutralising antibodies against emerging SARS-CoV-2 variants. EBioMedicine 2024; 110:105461. [PMID: 39612651 DOI: 10.1016/j.ebiom.2024.105461] [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: 06/18/2024] [Revised: 10/30/2024] [Accepted: 11/05/2024] [Indexed: 12/01/2024] Open
Abstract
BACKGROUND Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine. METHODS At baseline and 1-month post-booster, neutralisation activity and frequencies of receptor binding domain (RBD)-specific MBCs and Spike-specific memory T cells were measured against a panel of variants. FINDINGS Both vaccines boosted neutralising antibodies to 5 variants - Wuhan-Hu-1, Delta, BA.1, BA.5 and JN.1, the latter of which had not yet emerged at the time of sample collection. The bivalent vaccine induced a significantly larger increase in nAb against BA.1 and JN.1. Both vaccines boosted RBD-specific MBC responses to Wuhan-Hu-1, Delta, BA.1 and BA.5 variants with a significantly greater increase for BA.1 in the bivalent group. The breadth of MBCs was significantly higher in those who received the bivalent boost and correlated with nAb breadth. Both vaccines significantly boosted Spike-specific T cell responses to the Wuhan-Hu-1 and BA.5 variants, but only the bivalent vaccine boosted BA.1 responses. INTERPRETATION These results suggest that the bivalent vaccine confers an advantage against future novel variants due to increased frequency of broadly reactive RBD-specific B cells. FUNDING Work supported by NSW Health for the NSW Vaccine, Infection and Immunology Collaborative (VIIM).
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Affiliation(s)
- Lok Bahadur Shrestha
- The Kirby Institute, University of New South Wales, Sydney, NSW, Australia; School of Biomedical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW, Australia
| | - Katie Tungatt
- Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia
| | - Anupriya Aggarwal
- The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
| | - Aija Stubis
- Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia
| | - Nicole L Fewings
- Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia
| | - Christina Fichter
- The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
| | - Anouschka Akerman
- The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
| | - Chaturaka Rodrigo
- School of Biomedical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW, Australia
| | - Nicodemus Tedla
- School of Biomedical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW, Australia
| | - Sharon Lee
- Research & Education Network, Western Sydney Local Health District, Westmead, NSW, Australia
| | - Andrew R Lloyd
- The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
| | - Fabienne Brilot
- Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Westmead, NSW, Australia; Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
| | - Warwick J Britton
- Centenary Institute, The University of Sydney, Camperdown, NSW, Australia; RPAH Vaccination Centre, Sydney Local Health District, Sydney, NSW, Australia
| | - Anthony Kelleher
- The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
| | - Ian D Caterson
- RPAH Vaccination Centre, Sydney Local Health District, Sydney, NSW, Australia
| | - Mark W Douglas
- Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia; Storr Liver Centre, The Westmead Institute for Medical Research, Westmead, NSW, Australia; Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, NSW, Australia
| | - Rebecca Rockett
- Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
| | - Stuart G Tangye
- Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
| | - James A Triccas
- Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
| | - Stuart G Turville
- The Kirby Institute, University of New South Wales, Sydney, NSW, Australia
| | - Kerrie J Sandgren
- Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia; Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
| | - Rowena A Bull
- The Kirby Institute, University of New South Wales, Sydney, NSW, Australia; School of Biomedical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW, Australia
| | - Anthony L Cunningham
- Centre for Virus Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia; Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
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Oyebanji OA, Sundheimer N, Ragavapuram V, Wilson BM, Abul Y, Gravenstein S, Bosch J, King CL, Canaday DH. Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers. GeroScience 2024; 46:6183-6194. [PMID: 38789833 PMCID: PMC11493945 DOI: 10.1007/s11357-024-01215-y] [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: 02/22/2024] [Accepted: 05/17/2024] [Indexed: 05/26/2024] Open
Abstract
Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8 months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.
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Affiliation(s)
- Oladayo A Oyebanji
- Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Nicholas Sundheimer
- Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Vaishnavi Ragavapuram
- Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA
| | - Brigid M Wilson
- Geriatric Research Education and Clinical Center, Department of Veterans Affairs Medical Center, Louis Stokes Cleveland, Cleveland, OH, USA
| | - Yasin Abul
- Center of Innovation in Long-Term Services and Supports, Veterans Administration Medical Center, Providence, Rhode Island, USA
- Brown University School of Public Health Center for Gerontology and Healthcare Research, Providence, Rhode Island, USA
| | - Stefan Gravenstein
- Center of Innovation in Long-Term Services and Supports, Veterans Administration Medical Center, Providence, Rhode Island, USA
- Brown University School of Public Health Center for Gerontology and Healthcare Research, Providence, Rhode Island, USA
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Jürgen Bosch
- Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA
| | - Christopher L King
- Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA
| | - David H Canaday
- Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
- Geriatric Research Education and Clinical Center, Department of Veterans Affairs Medical Center, Louis Stokes Cleveland, Cleveland, OH, USA.
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Abuyadek R, Mousa M, AlAzazi J, Al Romaithi A, Selvaraj F, Alsafar H, Al Kaabi N, Al Hosani F. Genomic characteristics, disease outcome and heterologous vaccine effectiveness among cases with SARS CoV-2 infection. BMC Infect Dis 2024; 24:1266. [PMID: 39516737 PMCID: PMC11545176 DOI: 10.1186/s12879-024-10124-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND In the pursuit of global health security, continuous monitoring of vaccine effectiveness across various viral strains emerges as a crucial imperative. The emergence of SARS-CoV-2 major variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron, has added complexity to the COVID-19 vaccination landscape. OBJECTIVES To assess illness severity, evaluate vaccine efficacy across varying doses and types, and determine effectiveness against major VOCs within the population. METHODS This retrospective cohort study, conducted in Abu Dhabi, United Arab Emirates, focuses on a cohort of 44,073 SARS-CoV-2 positive cases from February 2021 to May 2022, dominated by the Delta and Omicron variants. The study employed a nested case-control design, analyzing hospital admissions for confirmed SARS-CoV-2 infection. RESULTS Vaccine effectiveness was higher among heterologus-boosted individuals at 87% (95% CI:79%-93%) compared to homologus-boosted individuals at 59% (95% CI: 48%-68%) and fully vaccinated, non-boosted adults at 53% (95% CI: 46%-59%). These findings highlight the importance of heterologous boosting, particularly against rapidly evolving viral variants, offering valuable insights for refining pandemic response strategies. CONCLUSION The study underscores the critical need for ongoing assessment and adaptation of vaccination strategies to the evolving viral landscape.
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Affiliation(s)
- Rowan Abuyadek
- Abu Dhabi Department of Health, Abu Dhabi Public Health Center, Abu Dhabi, United Arab Emirates
- High Institute of Public Health, Alexandria University, Alexandria, Egypt
| | - Mira Mousa
- Center for Biotechnology, Khalifa University, Abu Dhabi, UAE
- Department of Public Health and Epidemiology, College of Medicine and Health Science, Khalifa University, Abu Dhabi, UAE
| | | | - Ahmed Al Romaithi
- Department SKMC-CEO, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Francis Selvaraj
- Reference Laboratory for Infectious Disease (RLID), Department Laboratory Medicine Services, Sheikh Khalifa Medical City, PureLab, Abu Dhabi, United Arab Emirates
| | - Habiba Alsafar
- Center for Biotechnology, Khalifa University, Abu Dhabi, UAE
- Department of Biomedical Engineering and Biotechnology, College of Medicine and Health Science, Khalifa University, Abu Dhabi, UAE
| | - Nawal Al Kaabi
- College of Medicine and Health Science, Khalifa University, Abu Dhabi, UAE.
- Sheikh Khalifa Medical City, Abu Dhabi Health Services Company (SEHA), Abu Dhabi, United Arab Emirates.
| | - Farida Al Hosani
- Abu Dhabi Department of Health, Abu Dhabi Public Health Center, Abu Dhabi, United Arab Emirates
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8
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Itamochi M, Yazawa S, Saga Y, Shimada T, Tamura K, Maenishi E, Isobe J, Sasajima H, Kawashiri C, Tani H, Oishi K. COVID-19 mRNA booster vaccination induces robust antibody responses but few adverse events among SARS-CoV-2 naïve nursing home residents. Sci Rep 2024; 14:23295. [PMID: 39375365 PMCID: PMC11458568 DOI: 10.1038/s41598-024-73004-8] [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: 04/09/2024] [Accepted: 09/12/2024] [Indexed: 10/09/2024] Open
Abstract
Residents in nursing homes face heightened COVID-19 risks. We aimed to assess the adverse events (AEs) rates and antibody responses after the first to the fifth dose of COVID-19 mRNA vaccination in a nursing home cohort. Ninety-five SARS-CoV-2 naïve participants consisted of 26 staff (median age, 51 years) and 69 residents (median age, 88 years). Life-threatening AEs were reported in neither residents nor staff. The severity of non-life-threatening AEs was graded, and severe AEs were reported only in staff. The AEs rates were considerably lower in residents, compared to those in staff. Anti-RBD IgG and the neutralizing titers (NTs) against Wuhan and Omicron BA.4/BA.5 did not differ significantly between those with 'any AE' and 'no AE' among both staff and residents two months after the second, third and fifth doses, while the anti-RBD IgG significantly differed between two groups after third dose in residents. These findings suggest that the anti-RBD IgG and the NTs increase regardless of the occurrence of AEs. Our study underscores a robust antibody response in both in staff and residents, and fewer AEs following COVID-19 vaccination in SARS-CoV-2 naïve residents than staff, supporting the recommendation for mRNA booster doses in older adults at high-risk care facilities.
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Affiliation(s)
- Masae Itamochi
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Shunsuke Yazawa
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Yumiko Saga
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Takahisa Shimada
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Kosuke Tamura
- Department of Research Planning, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Emi Maenishi
- Department of Bacteriology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Junko Isobe
- Department of Bacteriology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Hitoshi Sasajima
- Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Chikako Kawashiri
- Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Hideki Tani
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan
| | - Kazunori Oishi
- Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama, 939-0363, Japan.
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9
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Smith CL, Didion E, Aung H, Tamilselvan B, Bej T, Oyebanji OA, Shive CL, Wilson BM, Cameron M, Cameron C, Gravenstein S, Canaday DH. Longitudinal Analysis of Nursing Home Residents' T-Cell Responses After SARS-CoV-2 mRNA Vaccinations Shows Influence of Biological Sex and Infection History. J Infect Dis 2024; 230:635-644. [PMID: 38743816 PMCID: PMC11420774 DOI: 10.1093/infdis/jiae234] [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: 12/07/2023] [Revised: 04/02/2024] [Accepted: 04/30/2024] [Indexed: 05/16/2024] Open
Abstract
BACKGROUND Vaccines and vaccine boosting have blunted excess morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in older nursing home residents (NHR). However, the impact of repeated vaccination on the T-cell response based on biological sex and prior infection of NHR remain understudied. METHODS We examined T-cell responses to SARS-CoV-2 mRNA vaccines in a cohort of NHR and healthcare workers (HCW) over 2 years. We used interferon-γ ELIspot and flow cytometry to assess T-cell response before, 2 weeks, and 6 months after the initial series and each of 2 booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T-cell effector function. RESULTS Prior SARS-CoV-2 infection and female sex contributed to higher T-cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T-cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations. CONCLUSIONS These results suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T-cell response to mRNA vaccination.
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Affiliation(s)
- Carson L Smith
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Elise Didion
- Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Htin Aung
- Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | | | - Taissa Bej
- Geriatric Research, Education, and Clinical Center, Louis Stokes Veterans Affairs Northeast Ohio Healthcare System, Cleveland, Ohio, USA
| | - Oladayo A Oyebanji
- Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Carey L Shive
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Geriatric Research, Education, and Clinical Center, Louis Stokes Veterans Affairs Northeast Ohio Healthcare System, Cleveland, Ohio, USA
| | - Brigid M Wilson
- Geriatric Research, Education, and Clinical Center, Louis Stokes Veterans Affairs Northeast Ohio Healthcare System, Cleveland, Ohio, USA
- Division of Infectious Diseases and HIV Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio, USA
| | - Mark Cameron
- Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA
| | - Cheryl Cameron
- Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, USA
| | - Stefan Gravenstein
- Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA
- Center on Innovation in Long-Term Services and Supports, Providence Veterans Administration Medical Center, Providence, Rhode Island, USA
| | - David H Canaday
- Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
- Geriatric Research, Education, and Clinical Center, Louis Stokes Veterans Affairs Northeast Ohio Healthcare System, Cleveland, Ohio, USA
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10
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Gravenstein S, DeVone F, Oyebanji OA, Abul Y, Cao Y, Chan PA, Halladay CW, Rudolph JL, Nugent C, Bosch J, King CL, Wilson BM, Balazs AB, White EM, Canaday DH, McConeghy KW. Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination. EBioMedicine 2024; 105:105180. [PMID: 38861869 PMCID: PMC11215210 DOI: 10.1016/j.ebiom.2024.105180] [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: 08/02/2023] [Revised: 05/12/2024] [Accepted: 05/17/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Bivalent SARS-CoV-2 vaccines were developed to counter increasing susceptibility to emerging SARS-CoV-2 variants. We evaluated the durability of immunity and protection following first bivalent vaccination among nursing home residents. METHODS We evaluated anti-spike and neutralization titers from blood in 653 community nursing home residents before and after each monovalent booster, and a bivalent vaccine. Concurrent clinical outcomes were evaluated using electronic health record data from a separate cohort of 3783 residents of Veterans Affairs (VA) nursing homes who had received at least the primary series monovalent vaccination. Using target trial emulation, we compared VA residents who did and did not receive the bivalent vaccine to measure vaccine effectiveness against infection, hospitalization, and death. FINDINGS In the community cohort, Omicron BA.5 neutralization activity rose after each monovalent and bivalent booster vaccination regardless of prior infection history. Titers declined over time but six months post-bivalent vaccination, BA.5 neutralization persisted at detectable levels in 75% of infection-naive and 98% of prior-infected individuals. In the VA nursing home cohort, bivalent vaccine added effectiveness to monovalent booster vaccination by 18.5% for infection (95% confidence interval (CI) -5.6, 34.0%), and 29.2% for hospitalization or death (95% CI -14.2, 56.2%) over five months. INTERPRETATION The level of protection declined after bivalent vaccination over a 6 month period and may open a window of added vulnerability before the next updated vaccine becomes available, suggesting a subset of nursing home residents may benefit from an additional vaccination booster. FUNDING CDC, NIH, VHA.
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Affiliation(s)
- Stefan Gravenstein
- Warren Alpert Medical School, Brown University, Providence, RI, USA; Department of Health Services, Policy & Practice, School of Public Health, Brown University, Providence, RI, USA; Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, RI, USA.
| | - Frank DeVone
- Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, RI, USA
| | | | - Yasin Abul
- Warren Alpert Medical School, Brown University, Providence, RI, USA; Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, RI, USA
| | - Yi Cao
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
| | - Philip A Chan
- Warren Alpert Medical School, Brown University, Providence, RI, USA; Rhode Island Department of Health, Providence, RI, USA
| | - Christopher W Halladay
- Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, RI, USA
| | - James L Rudolph
- Warren Alpert Medical School, Brown University, Providence, RI, USA; Department of Health Services, Policy & Practice, School of Public Health, Brown University, Providence, RI, USA; Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, RI, USA
| | - Clare Nugent
- Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Jürgen Bosch
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | | | - Brigid M Wilson
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA
| | | | - Elizabeth M White
- Department of Health Services, Policy & Practice, School of Public Health, Brown University, Providence, RI, USA
| | - David H Canaday
- Case Western Reserve University School of Medicine, Cleveland, OH, USA; Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA.
| | - Kevin W McConeghy
- Department of Health Services, Policy & Practice, School of Public Health, Brown University, Providence, RI, USA; Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, RI, USA.
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11
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Sánchez-Simarro Á, Fernández-Soto D, Grau B, Albert E, Giménez E, Avilés-Alía AI, Gozalbo-Rovira R, Rusu L, Olea B, Geller R, Reyburn HT, Navarro D. Functional antibody responses targeting the Spike protein of SARS-CoV-2 Omicron XBB.1.5 in elderly nursing home residents following Wuhan-Hu-1-based mRNA booster vaccination. Sci Rep 2024; 14:11896. [PMID: 38789475 PMCID: PMC11126592 DOI: 10.1038/s41598-024-62874-7] [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: 02/15/2024] [Accepted: 05/22/2024] [Indexed: 05/26/2024] Open
Abstract
The immune effector mechanisms involved in protecting against severe COVID-19 infection in elderly nursing home residents following vaccination or natural infection are not well understood. Here, we measured SARS-CoV-2 Spike (S)-directed functional antibody responses, including neutralizing antibodies (NtAb) and antibody Fc-mediated NK cell activity (degranulation and IFNγ production), against the Wuhan-Hu-1, BA.4/5 (for NtAb), and Omicron XBB.1.5 variants in elderly nursing home residents (n = 39; median age, 91 years) before and following a third (pre- and post-3D) and a fourth (pre- and post-4D) mRNA COVID-19 vaccine dose. Both 3D and 4D boosted NtAb levels against both (sub)variants. Likewise, 3D and 4D increased the ability of sera to trigger both LAMP1- and IFNγ-producing NK cells, in particular against XBB.1.5. In contrast to NtAb titres, the frequencies of LAMP1- and IFNγ-producing NK cells activated by antibodies binding to Wuhan-Hu-1 and Omicron XBB.1.5 S were comparable at all testing times. Stronger functional antibody responses were observed in vaccine-experienced participants compared to vaccine-naïve at some testing times. These findings can contribute to identifying a reliable correlate of protection in elderly nursing home residents against severe COVID-19 and inform future vaccine strategies in this population group.
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Grants
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- FIS, PI21/00563 Instituto de Salud Carlos III
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- 202020E079 y CSIC-COVID19-028 Fundación General CSIC
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
- PID2020-115506RB-I00 (HTR) Ministerio de Ciencia e Innovación
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Affiliation(s)
- Ángela Sánchez-Simarro
- Microbiology Service, Clinic University Hospital, INCLIVA Health Research Institute, Av. Blasco Ibáñez 17, 46010, Valencia, Spain
| | - Daniel Fernández-Soto
- Department of Immunology and Oncology, National Centre for Biotechnology, CNB-CSIC, Madrid, Spain
| | - Brayan Grau
- Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, 46980, Valencia, Spain
| | - Eliseo Albert
- Microbiology Service, Clinic University Hospital, INCLIVA Health Research Institute, Av. Blasco Ibáñez 17, 46010, Valencia, Spain
| | - Estela Giménez
- Microbiology Service, Clinic University Hospital, INCLIVA Health Research Institute, Av. Blasco Ibáñez 17, 46010, Valencia, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - Ana Isabel Avilés-Alía
- Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, 46980, Valencia, Spain
| | | | - Luciana Rusu
- Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, 46980, Valencia, Spain
| | - Beatriz Olea
- Microbiology Service, Clinic University Hospital, INCLIVA Health Research Institute, Av. Blasco Ibáñez 17, 46010, Valencia, Spain
| | - Ron Geller
- Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, 46980, Valencia, Spain
| | - Hugh T Reyburn
- Department of Immunology and Oncology, National Centre for Biotechnology, CNB-CSIC, Madrid, Spain
| | - David Navarro
- Microbiology Service, Clinic University Hospital, INCLIVA Health Research Institute, Av. Blasco Ibáñez 17, 46010, Valencia, Spain.
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
- Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain.
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12
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Chisty ZA, Li DD, Haile M, Houston H, DaSilva J, Overton R, Schuh AJ, Haynie J, Clemente J, Branch AG, Arons MM, Tsang CA, Pellegrini GJ, Bugrysheva J, Ilutsik J, Mohelsky R, Comer P, Hundia SB, Oh H, Stuckey MJ, Bohannon CD, Rasheed MAU, Epperson M, Thornburg NJ, McDonald LC, Brown AC, Kutty PK. Immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination among nursing home residents-Georgia, October 2020-July 2022. PLoS One 2024; 19:e0301367. [PMID: 38625908 PMCID: PMC11020945 DOI: 10.1371/journal.pone.0301367] [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: 11/20/2023] [Accepted: 03/07/2024] [Indexed: 04/18/2024] Open
Abstract
BACKGROUND Understanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population. METHODS An observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay. RESULTS The median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt. CONCLUSIONS These findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape.
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Affiliation(s)
- Zeshan A. Chisty
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Deana D. Li
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Melia Haile
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Hollis Houston
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Juliana DaSilva
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Rahsaan Overton
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Amy J. Schuh
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Jenn Haynie
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
- Goldbelt C6, LLC, Chesapeake, Virginia, United States of America
| | - Jacob Clemente
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Alicia G. Branch
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Melissa M. Arons
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Clarisse A. Tsang
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Gerald J. Pellegrini
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Julia Bugrysheva
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Justina Ilutsik
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
- Goldbelt C6, LLC, Chesapeake, Virginia, United States of America
| | - Romy Mohelsky
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Patricia Comer
- A.G. Rhodes Wesley Woods Heath and Rehab, Atlanta, Georgia, United States of America
| | | | - Hyungseok Oh
- Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - Matthew J. Stuckey
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Caitlin D. Bohannon
- Coronavirus and Other Respiratory Viruses Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Mohammed Ata Ur Rasheed
- Coronavirus and Other Respiratory Viruses Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Monica Epperson
- Coronavirus and Other Respiratory Viruses Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Natalie J. Thornburg
- Coronavirus and Other Respiratory Viruses Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - L. Clifford McDonald
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Allison C. Brown
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Preeta K. Kutty
- COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
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13
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Abul Y, Nugent C, Vishnepolskiy I, Wallace T, Dickerson E, Holland L, Esparza I, Winkis M, Wali KT, Chan PA, Baier RR, Recker A, Kaczynski M, Kamojjala S, Pralea A, Rice H, Osias O, Oyebanji OA, Olagunju O, Cao Y, Li CJ, Roederer A, Pfeifer WM, King CL, Bosch J, Nanda A, McNicoll L, Mujahid N, Raza S, Tyagi R, Wilson BM, White EM, Canaday DH, Gravenstein S, Balazs AB. Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.03.21.24303684. [PMID: 38585784 PMCID: PMC10996740 DOI: 10.1101/2024.03.21.24303684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
Background SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Methods The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. Results The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection. Conclusion The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination. Impact Statement All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake. Key Points Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.
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Roederer AL, Cao Y, Denis KS, Sheehan ML, Li CJ, Lam EC, Gregory DJ, Poznansky MC, Iafrate AJ, Canaday DH, Gravenstein S, Garcia-Beltran WF, Balazs AB. Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.03.05.24303815. [PMID: 38496628 PMCID: PMC10942518 DOI: 10.1101/2024.03.05.24303815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.
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Affiliation(s)
- Alex L. Roederer
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
| | - Yi Cao
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
| | - Kerri St. Denis
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
| | | | - Chia Jung Li
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
| | - Evan C. Lam
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
| | - David J. Gregory
- Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA, 02129, USA
- Pediatric Infectious Disease, Massachusetts General Hospital for Children, Boston, MA 02114, USA
| | - Mark C. Poznansky
- Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA, 02129, USA
- Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA
| | - A. John Iafrate
- Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - David H. Canaday
- Case Western Reserve University School of Medicine, Cleveland, OH
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio
| | - Stefan Gravenstein
- Center of Innovation in Long-Term Services and Supports, Veterans Administration Medical Center, Providence, Rhode Island
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA
- Brown University School of Public Health Center for Gerontology and Healthcare Research, Providence, Rhode Island
| | - Wilfredo F. Garcia-Beltran
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA
- Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA
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Wagatsuma K, Saito R, Yoshioka S, Yamazaki S, Sato R, Iwaya M, Takahashi Y, Chon I, Naito M, Watanabe H. Anti-SARS-CoV-2 IgG antibody after the second and third mRNA vaccinations in staff and residents in a nursing home with a previous COVID-19 outbreak in Niigata, Japan. J Infect Chemother 2024; 30:164-168. [PMID: 37739181 DOI: 10.1016/j.jiac.2023.09.021] [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: 06/16/2023] [Revised: 09/06/2023] [Accepted: 09/17/2023] [Indexed: 09/24/2023]
Abstract
This study measured IgG antibody titers against spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 before vaccination and after the second and third doses of an mRNA vaccine in staff and residents of a nursing home in Niigata, Japan. The study included 52 staff members, of whom six (11.5%) were previously infected with SARS-CoV-2, and 32 older residents, of whom 22 (68.8%) were previously infected. All participants received the first two doses in April-July 2021 and a third dose in January-March 2022. In staff, the median anti-S antibody titers (interquartile range) in previously infected and SARS-CoV-2-naïve individuals before vaccination were 960 (592-1,926) and 0.5 (0.0-2.1) arbitrary units (AU)/mL. Anti-S antibody titers 5 months after the second and third doses in previously infected staff were 7,391 (5,230-7,747) and 10,195 (5,582-13,886) AU. In residents, the median anti-S antibody titers in previously infected and naïve individuals before vaccination were 734 (425-1,934) and 1.1 (0.0-3.1) AU/mL. Anti-S antibody titers at 5 months after the second and third doses in previously infected residents were 15,872 (9,683-21,557) and 13,813 (6,689-20,839) AU/mL; however, there were no significant differences in titers between the second and third doses in previously infected residents. Anti-N antibody titers were higher in previously infected than naïve individuals, and titers decreased chronologically.
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Affiliation(s)
- Keita Wagatsuma
- Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; Japan Society for the Promotion of Science, Tokyo, Japan.
| | - Reiko Saito
- Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Sayaka Yoshioka
- Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Satoru Yamazaki
- Niigata City Public Health and Sanitation Center, Niigata, Japan
| | - Ryosuke Sato
- Niigata City Public Health and Sanitation Center, Niigata, Japan
| | - Masako Iwaya
- Niigata City Public Health and Sanitation Center, Niigata, Japan
| | | | - Irina Chon
- Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | | | - Hisami Watanabe
- Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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Oyebanji OA, Abul Y, Wilson BM, Bosch J, Didion EM, Paxitzis AN, Sundheimer N, Ragavapuram V, Wilk D, Keresztesy D, Aung H, Cao Y, King CL, Balazs AB, White EM, Gravenstein S, Canaday DH. Neutralization and binding antibody response to second bivalent COVID-19 vaccination in nursing home residents. J Am Geriatr Soc 2023; 71:3947-3950. [PMID: 37589423 PMCID: PMC10840677 DOI: 10.1111/jgs.18557] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 07/20/2023] [Indexed: 08/18/2023]
Affiliation(s)
| | - Yasin Abul
- Center of Innovation in Long-Term Services and Supports, Veterans Administration Medical Center, Providence, RI
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI
| | - Brigid M. Wilson
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH
| | | | | | | | | | | | | | | | | | | | | | | | | | - Stefan Gravenstein
- Center of Innovation in Long-Term Services and Supports, Veterans Administration Medical Center, Providence, RI
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI
- Brown University School of Public Health Center for Gerontology and Healthcare Research, Providence, RI
| | - David H. Canaday
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH
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Eybpoosh S, Biglari A, Sorouri R, Ashrafian F, Sadat Larijani M, Verez-Bencomo V, Toledo-Romani ME, Valenzuela Silva C, Salehi-Vaziri M, Dahmardeh S, Doroud D, Banifazl M, Mostafavi E, Bavand A, Ramezani A. Immunogenicity and safety of heterologous boost immunization with PastoCovac Plus against COVID-19 in ChAdOx1-S or BBIBP-CorV primed individuals. PLoS Pathog 2023; 19:e1011744. [PMID: 37910480 PMCID: PMC10619776 DOI: 10.1371/journal.ppat.1011744] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 10/10/2023] [Indexed: 11/03/2023] Open
Abstract
BACKGROUND This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV. MATERIALS AND METHODS 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into two heterologous regimens receiving a third dose of PastoCovac Plus, and two parallel homologous groups receiving the third dose of BBIBP-CorV or ChAdOx1-S. Serum samples were obtained just before and 4 weeks after booster dose. Anti-spike IgG and neutralizing antibodies were quantified and the conventional live-virus neutralization titer, (cVNT50) assay was done against Omicron BA.5 variant. Moreover, the adverse events data were recorded after receiving booster doses. RESULTS ChAdOx1-S/PastoCovac Plus group reached 73.0 units increase in anti-Spike IgG rise compared to the ChAdOx1-S/ ChAdOx1-S (P: 0.016). No significant difference was observed between the two groups regarding neutralizing antibody rise (P: 0.256), indicating equivalency of both booster types. Adjusting for baseline titers, the BBIBP-CorV/PastoCovac Plus group showed 135.2 units increase (P<0.0001) in anti-Spike IgG, and 3.1 (P: 0.008) unit increase in mean rise of neutralizing antibodies compared to the homologous group. Adjustment for COVID-19 history, age, underlying diseases, and baseline antibody titers increased the odds of anti-Spike IgG fourfold rise both in the ChAdOx1-S (OR: 1.9; P: 0.199) and BBIBP CorV (OR: 37.3; P< 0.0001) heterologous groups compared to their corresponding homologous arms. The odds of neutralizing antibody fourfold rise, after adjustment for the same variables, was 2.4 (P: 0.610) for the ChAdOx1-S heterologous group and 5.4 (P: 0.286) for the BBIBP CorV heterologous groups compared to their corresponding homologous groups. All the booster types had the potency to neutralize BA.5 variant with no significant difference. The highest rate of adverse event incidence was recorded for ChAdOx1-S homologous group. CONCLUSIONS PastoCovac Plus booster application in primed individuals with BBIBP-CorV or ChAdOx1-S successfully increased specific antibodies' levels without any serious adverse events. This vaccine could be administrated in the heterologous regimen to effectively boost humoral immune responses.
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Affiliation(s)
- Sana Eybpoosh
- Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| | - Alireza Biglari
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Rahim Sorouri
- IPI Directorate, Pasteur Institute of Iran, Tehran, Iran
- Department of Microbiology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Fatemeh Ashrafian
- Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
| | | | | | | | | | | | - Sarah Dahmardeh
- Vaccination Department, Pasteur Institute of Iran, Tehran, Iran
| | - Delaram Doroud
- Quality Control Department, Production and research Complex, Pasteur Institute of Iran, Tehran, Iran
| | - Mohammad Banifazl
- Iranian Society for Support of Patients with Infectious Disease, Tehran, Iran
| | - Ehsan Mostafavi
- Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| | - Anahita Bavand
- Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
| | - Amitis Ramezani
- Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
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Dalla Gasperina D, Veronesi G, Castelletti CM, Varchetta S, Ottolini S, Mele D, Ferrari G, Shaik AKB, Celesti F, Dentali F, Accolla RS, Forlani G. Humoral and Cellular Immune Response Elicited by the BNT162b2 COVID-19 Vaccine Booster in Elderly. Int J Mol Sci 2023; 24:13728. [PMID: 37762029 PMCID: PMC10530943 DOI: 10.3390/ijms241813728] [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: 08/04/2023] [Revised: 08/22/2023] [Accepted: 08/26/2023] [Indexed: 09/29/2023] Open
Abstract
Although the safety and efficacy of COVID-19 vaccines in older people are critical to their success, little is known about their immunogenicity among elderly residents of long-term care facilities (LTCFs). A single-center prospective cohort study was conducted: a total IgG antibody titer, neutralizing antibodies against Wild-type, Delta Plus, and Omicron BA.2 variants and T cell response, were measured eight months after the second dose of BNT162b2 vaccine (T0) and at least 15 days after the booster (T1). Forty-nine LTCF residents, with a median age of 84.8 ± 10.6 years, were enrolled. Previous COVID-19 infection was documented in 42.9% of the subjects one year before T0. At T1, the IgG titers increased up to 10-fold. This ratio was lower in the subjects with previous COVID-19 infection. At T1, IgG levels were similar in both groups. The neutralizing activity against Omicron BA.2 was significantly lower (65%) than that measured against Wild-type and Delta Plus (90%). A significant increase of T cell-specific immune response was observed after the booster. Frailty, older age, sex, cognitive impairment, and comorbidities did not affect antibody titers or T cell response. In the elderly sample analyzed, the BNT162b2 mRNA COVID-19 vaccine produced immunogenicity regardless of frailty.
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Affiliation(s)
- Daniela Dalla Gasperina
- Department of Medicine and Technological Innovation, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy;
| | - Giovanni Veronesi
- Research Centre in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy;
| | | | - Stefania Varchetta
- Clinical Immunology-Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Sabrina Ottolini
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy;
| | - Dalila Mele
- Microbiology and Molecular Virology Unit, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, Italy;
| | | | - Amruth K. B. Shaik
- Laboratory of General Pathology and Immunology “Giovanna Tosi”, Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy; (A.K.B.S.); (R.S.A.)
| | - Fabrizio Celesti
- Center for Immuno-Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy;
| | - Francesco Dentali
- Department of Medicine and Surgery, University of Insubria, ASST Sette Laghi, 21100 Varese, Italy;
| | - Roberto S. Accolla
- Laboratory of General Pathology and Immunology “Giovanna Tosi”, Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy; (A.K.B.S.); (R.S.A.)
| | - Greta Forlani
- Laboratory of General Pathology and Immunology “Giovanna Tosi”, Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy; (A.K.B.S.); (R.S.A.)
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Chong Y, Goto T, Watanabe H, Tani N, Yonekawa A, Ikematsu H, Shimono N, Tanaka Y, Akashi K. Achievement of sufficient antibody response after a fourth dose of wild-type SARS-CoV-2 mRNA vaccine in nursing home residents. Immun Inflamm Dis 2023; 11:e962. [PMID: 37647452 PMCID: PMC10461422 DOI: 10.1002/iid3.962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 07/09/2023] [Accepted: 07/13/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND Infection control during COVID-19 outbreaks in nursing facilities is a critical public health issue. Antibody responses before and after the fourth (second booster) dose of wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in nursing home residents have not been fully characterized. METHODS This study included 112 individuals: 54 nursing home residents (mean age: 84.4 years; 35 SARS-CoV-2-naive and 19 previously infected) and 58 healthcare workers (mean age: 47.7 years; 25 SARS-CoV-2-naive and 33 previously infected). Antispike and antinucleocapsid antibody responses to messenger RNA vaccination were evaluated using serum samples collected shortly and 5 months after the third dose, and shortly after the fourth dose. RESULTS The median immunoglobulin G (IgG) level in SARS-CoV-2-naive residents was similar to that in SARS-CoV-2-naive healthcare workers after the fourth dose (24,026.3 vs. 30,328.6 AU/mL, p = .79), whereas after the third dose the IgG level of SARS-CoV-2-naive residents was approximately twofold lower than that in SARS-CoV-2-naive healthcare workers. In residents with previous SARS-CoV-2 infection, timing of infection in relation to vaccination affected the kinetics of antibody responses. Residents infected after the third dose showed the highest IgG levels after the fourth dose among all groups (median: 64,328.8 AU/mL), in contrast to residents infected before initiating vaccination with antibody levels similar to those of SARS-CoV-2-naive residents. CONCLUSIONS Advanced aged nursing home residents, poor responders in the initial SARS-CoV-2 vaccine series, could achieve sufficient antibody responses after the fourth (second booster) vaccination, comparable to those of younger adults.
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Affiliation(s)
- Yong Chong
- Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine)FukuokaJapan
| | - Takeyuki Goto
- Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine)FukuokaJapan
| | - Haruka Watanabe
- Department of Clinical Immunology, Rheumatology, and Infectious DiseaseKyushu University HospitalFukuokaJapan
| | - Naoki Tani
- Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine)FukuokaJapan
| | - Akiko Yonekawa
- Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine)FukuokaJapan
| | - Hideyuki Ikematsu
- Division of Influenza ResearchJapan Physicians AssociationTokyoJapan
| | - Nobuyuki Shimono
- Department of Center for the Study of Global InfectionCenter for the Study of Global Infection, Kyushu University HospitalFukuokaJapan
| | - Yosuke Tanaka
- Department of Internal MedicineMedical Corporation SOUSEIKAI, Kanenokuma HospitalFukuokaJapan
| | - Koichi Akashi
- Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine)FukuokaJapan
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Ramezani A, Sorouri R, Haji Maghsoudi S, Dahmardeh S, Doroud D, Sadat Larijani M, Eybpoosh S, Mostafavi E, Olyaeemanesh A, Salehi-Vaziri M, Bavand A, Zarghani G, Moradi L, Ashrafian F, Bagheri Amiri F, Mashayekhi P, Tahmasebi Z, Biglari A. PastoCovac and PastoCovac Plus as protein subunit COVID-19 vaccines led to great humoral immune responses in BBIP-CorV immunized individuals. Sci Rep 2023; 13:8065. [PMID: 37202438 PMCID: PMC10195798 DOI: 10.1038/s41598-023-35147-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 05/13/2023] [Indexed: 05/20/2023] Open
Abstract
The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals who were previously primed with BBIBP-CorV vaccines were divided into three arms on their choice as heterologous regimens BBIBP-CorV/PastoCovac (n = 68), BBIBP-CorV/PastoCovac Plus (n = 72) and homologous BBIBP-CorV (n = 74). PastoCovac booster recipients achieved the highest rate of anti-Spike IgG titer rise with a fourfold rise in 50% of the group. Anti-RBD IgG and neutralizing antibody mean rise and fold rise were almost similar between the PastoCovac and PastoCovac Plus booster receivers. The antibody durability results indicated that the generated antibodies were persistent until day 180 in all three groups. Nevertheless, a higher rate of antibody titer was seen in the heterologous regimen compared to BBIP-CorV group. Furthermore, no serious adverse event was recorded. The protein subunit-based booster led to a stronger humoral immune response in comparison with the BBIP-CorV booster receivers. Both the protein subunit boosters neutralized SARS-CoV-2 significantly more than BBIP-CorV. Notably, PastoCovac protein subunit-based vaccine could be successfully applied as a booster with convenient immunogenicity and safety profile.
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Affiliation(s)
- Amitis Ramezani
- Clinical Research Department, Pasteur Institute of Iran, No 69, Pasteur Ave., Tehran, Iran
| | - Rahim Sorouri
- IPI Directorate, Pasteur Institute of Iran, Tehran, Iran
| | - Saiedeh Haji Maghsoudi
- Modeling in Health Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
- Department of Biostatistics and Epidemiology, School of Public Health, Kerman University of Medical Sciences, Kerman, Iran
| | - Sarah Dahmardeh
- Department of Vaccination, Pasteur Institute of Iran, Tehran, Iran
| | - Delaram Doroud
- Quality Control Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran
| | - Mona Sadat Larijani
- Clinical Research Department, Pasteur Institute of Iran, No 69, Pasteur Ave., Tehran, Iran.
| | - Sana Eybpoosh
- Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| | - Ehsan Mostafavi
- Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| | - Alireza Olyaeemanesh
- Health Equity Research Centre and National Institute of Health Research, Tehran University of Medical Science, Tehran, Iran
| | | | - Anahita Bavand
- Clinical Research Department, Pasteur Institute of Iran, No 69, Pasteur Ave., Tehran, Iran
| | | | - Ladan Moradi
- Clinical Research Department, Pasteur Institute of Iran, No 69, Pasteur Ave., Tehran, Iran
| | - Fatemeh Ashrafian
- Clinical Research Department, Pasteur Institute of Iran, No 69, Pasteur Ave., Tehran, Iran
| | - Fahimeh Bagheri Amiri
- Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| | - Parisa Mashayekhi
- Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Zahra Tahmasebi
- Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| | - Alireza Biglari
- School of Medicine, Tehran University of Medical Sciences, Enghelab Street, P.O. BOX 14155-6559, Tehran, Iran.
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Bulgaresi M, Rivasi G, Tarantini F, Espinoza Tofalos S, Del Re LM, Salucci C, Turrin G, Barucci R, Bandinelli C, Fattorini L, Borchi D, Betti M, Checchi S, Baggiani L, Collini F, Lorini C, Bonaccorsi G, Ungar A, Mossello E, Benvenuti E. Impact of SARS-CoV2 infection on mortality and hospitalization in nursing home residents during the "Omicron era". Aging Clin Exp Res 2023; 35:1393-1399. [PMID: 37103663 PMCID: PMC10134704 DOI: 10.1007/s40520-023-02415-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 04/12/2023] [Indexed: 04/28/2023]
Abstract
BACKGROUND Widespread vaccination and emergence of less aggressive SARS-CoV2 variants may have blunted the unfavourable outcomes of COVID-19 in nursing home (NH) residents. We analysed the course of COVID-19 epidemic in NHs of Florence, Italy, during the "Omicron era" and investigated the independent effect of SARS-CoV2 infection on death and hospitalization risk. METHODS Weekly SARS-CoV2 infection rates between November 2021 and March 2022 were calculated. Detailed clinical data were collected in a sample of NHs. RESULTS Among 2044 residents, 667 SARS-CoV2 cases were confirmed. SARS-CoV2 incidence sharply increased during the Omicron era. Mortality rates did not differ between SARS-CoV2-positive (6.9%) and SARS-CoV2-negative residents (7.3%, p = 0.71). Chronic obstructive pulmonary disease and poor functional status, but not SARS-CoV2 infection independently predicted death and hospitalization. CONCLUSIONS Despite that SARS-CoV2 incidence increased during the Omicron era, SARS-CoV2 infection was not a significant predictor of hospitalization and death in the NH setting.
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Affiliation(s)
- Matteo Bulgaresi
- Geriatric Unit, Local Health Unit "Toscana Centro", Santa Maria Annunziata Hospital, Florence, Italy
| | - Giulia Rivasi
- Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy.
| | - Francesca Tarantini
- Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Sofia Espinoza Tofalos
- Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Lorenzo Maria Del Re
- Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Caterina Salucci
- Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Giada Turrin
- Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Riccardo Barucci
- Geriatric Unit, Local Health Unit "Toscana Centro", Santa Maria Annunziata Hospital, Florence, Italy
| | - Chiara Bandinelli
- Geriatric Unit, Local Health Unit "Toscana Centro", Santa Maria Annunziata Hospital, Florence, Italy
| | - Letizia Fattorini
- Department of Health Science, University of Florence, Florence, Italy
| | - Daniele Borchi
- Department of Health Science, University of Florence, Florence, Italy
| | - Marta Betti
- Department of Health Science, University of Florence, Florence, Italy
| | - Saverio Checchi
- Department of Health Science, University of Florence, Florence, Italy
| | - Lorenzo Baggiani
- Department of Community Healthcare Network, Health District "Toscana Centro", Florence, Italy
| | - Francesca Collini
- Quality and Equity Unit, Regional Health Agency of Tuscany, 50141, Florence, Italy
| | - Chiara Lorini
- Department of Health Science, University of Florence, Florence, Italy
| | | | - Andrea Ungar
- Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Enrico Mossello
- Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Enrico Benvenuti
- Geriatric Unit, Local Health Unit "Toscana Centro", Santa Maria Annunziata Hospital, Florence, Italy
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22
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Gravenstein S, DeVone F, Oyebanji OA, Abul Y, Cao Y, Chan PA, Halladay CW, McConeghy KW, Nugent C, Bosch J, King CL, Wilson BM, Balazs AB, White EM, Canaday DH. Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.04.25.23289050. [PMID: 37163130 PMCID: PMC10168517 DOI: 10.1101/2023.04.25.23289050] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Background Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents. Methods For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine. Results We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost. Conclusion Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents.
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Affiliation(s)
- Stefan Gravenstein
- Warren Alpert Medical School, Brown University, Providence, RI
- Department of Health Services, Policy & Practice, School of Public Health, Brown University, Providence, Rhode Island
- Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, Rhode Island
| | - Frank DeVone
- Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, Rhode Island
| | | | - Yasin Abul
- Warren Alpert Medical School, Brown University, Providence, RI
- Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, Rhode Island
| | - Yi Cao
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA
| | - Philip A Chan
- Warren Alpert Medical School, Brown University, Providence, RI
- Rhode Island Department of Health, Providence, RI
| | - Christopher W Halladay
- Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, Rhode Island
| | - Kevin W McConeghy
- Center of Innovation in Long-Term Services and Supports, Veterans Administration (VA) Medical Center, Providence, Rhode Island
| | - Clare Nugent
- Warren Alpert Medical School, Brown University, Providence, RI
| | - Jürgen Bosch
- Case Western Reserve University School of Medicine, Cleveland, OH
| | | | - Brigid M Wilson
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio
| | | | - Elizabeth M White
- Warren Alpert Medical School, Brown University, Providence, RI
- Department of Health Services, Policy & Practice, School of Public Health, Brown University, Providence, Rhode Island
| | - David H Canaday
- Case Western Reserve University School of Medicine, Cleveland, OH
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio
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23
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Yang L, Van Beek M, Wang Z, Muecksch F, Canis M, Hatziioannou T, Bieniasz PD, Nussenzweig MC, Chakraborty AK. Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain. Cell Rep 2023; 42:112256. [PMID: 36952347 PMCID: PMC9986127 DOI: 10.1016/j.celrep.2023.112256] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 11/07/2022] [Accepted: 02/27/2023] [Indexed: 03/08/2023] Open
Abstract
The Omicron variant of SARS-CoV-2 is not effectively neutralized by most antibodies elicited by two doses of mRNA vaccines, but a third dose increases anti-Omicron neutralizing antibodies. We reveal mechanisms underlying this observation by combining computational modeling with data from vaccinated humans. After the first dose, limited antigen availability in germinal centers (GCs) results in a response dominated by B cells that target immunodominant epitopes that are mutated in an Omicron-like variant. After the second dose, these memory cells expand and differentiate into plasma cells that secrete antibodies that are thus ineffective for such variants. However, these pre-existing antigen-specific antibodies transport antigen efficiently to secondary GCs. They also partially mask immunodominant epitopes. Enhanced antigen availability and epitope masking in secondary GCs together result in generation of memory B cells that target subdominant epitopes that are less mutated in Omicron. The third dose expands these cells and boosts anti-variant neutralizing antibodies.
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Affiliation(s)
- Leerang Yang
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Matthew Van Beek
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Zijun Wang
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
| | - Frauke Muecksch
- Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
| | - Marie Canis
- Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
| | | | - Paul D Bieniasz
- Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA
| | - Michel C Nussenzweig
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
| | - Arup K Chakraborty
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
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24
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Nugent C, Abul Y, White EM, Shehadeh F, Kaczynski M, Oscar Felix L, Ganesan N, Oyebanji OA, Vishnepolskiy I, Didion EM, Paxitzis A, Sheehan ML, Chan PA, Pfeifer WM, Dickerson E, Kamojjala S, Wilson BM, Mylonakis E, King CL, Balazs AB, Canaday DH, Gravenstein S. Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers. Vaccine 2023; 41:3403-3409. [PMID: 37117056 PMCID: PMC10123357 DOI: 10.1016/j.vaccine.2023.04.034] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 04/04/2023] [Accepted: 04/11/2023] [Indexed: 04/30/2023]
Abstract
We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 376 NH residents and 63 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain, Omicron BA.1 and BA.5 variants. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over 3-6 months. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 8.1 (95% CI 4.4, 14.8) and 7.8 (95% CI 4.8, 12.9) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p < 0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up-to-date on recommended SARS-CoV-2 vaccine booster doses.
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Affiliation(s)
- Clare Nugent
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI, United States
| | - Yasin Abul
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI, United States; Center on Innovation in Long-Term Services and Supports, Providence Veterans Administration Medical Center, Providence, RI, United States; Brown University School of Public Health Center for Gerontology and Healthcare Research, Providence, RI, United States
| | - Elizabeth M White
- Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, RI, United States
| | - Fadi Shehadeh
- Division of Infectious Diseases, Alpert Medical School of Brown University, Providence, RI, United States
| | - Matthew Kaczynski
- Division of Infectious Diseases, Alpert Medical School of Brown University, Providence, RI, United States
| | - Lewis Oscar Felix
- Division of Infectious Diseases, Alpert Medical School of Brown University, Providence, RI, United States
| | - Narchonai Ganesan
- Division of Infectious Diseases, Alpert Medical School of Brown University, Providence, RI, United States
| | - Oladayo A Oyebanji
- Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Igor Vishnepolskiy
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI, United States; Center on Innovation in Long-Term Services and Supports, Providence Veterans Administration Medical Center, Providence, RI, United States
| | - Elise M Didion
- Geriatric Research, Education and Clinical Center, VA Northeast Ohio Healthcare System, Cleveland VA, United States
| | - Alexandra Paxitzis
- Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Maegan L Sheehan
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States
| | - Philip A Chan
- Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, RI, United States
| | | | - Evan Dickerson
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI, United States; Center on Innovation in Long-Term Services and Supports, Providence Veterans Administration Medical Center, Providence, RI, United States
| | - Shreya Kamojjala
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI, United States
| | - Brigid M Wilson
- Case Western Reserve University School of Medicine, Cleveland, OH, United States; Geriatric Research, Education and Clinical Center, VA Northeast Ohio Healthcare System, Cleveland VA, United States
| | - Eleftherios Mylonakis
- Division of Infectious Diseases, Alpert Medical School of Brown University, Providence, RI, United States
| | - Christopher L King
- Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | | | - David H Canaday
- Case Western Reserve University School of Medicine, Cleveland, OH, United States; Geriatric Research, Education and Clinical Center, VA Northeast Ohio Healthcare System, Cleveland VA, United States.
| | - Stefan Gravenstein
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, RI, United States; Center on Innovation in Long-Term Services and Supports, Providence Veterans Administration Medical Center, Providence, RI, United States; Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, RI, United States.
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25
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Third dose of COVID-19 mRNA vaccine closes the gap in immune response between naïve nursing home residents and healthy adults. Vaccine 2023; 41:2829-2836. [PMID: 36997386 PMCID: PMC10040352 DOI: 10.1016/j.vaccine.2023.03.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/15/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023]
Abstract
Background Nursing home residents, a frail and old population group, respond poorly to primary mRNA COVID-19 vaccination. A third dose has been shown to boost protection against severe disease and death in this immunosenescent population, but limited data is available on the immune responses it induces. Methods In this observational cohort study, peak humoral and cellular immune responses were compared 28 days after the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in residents and staff members of two Belgian nursing homes. Only individuals without evidence of previous SARS-CoV-2 infection at third dose administration were included in the study. In addition, an extended cohort of residents and staff members was tested for immune responses to a third vaccine dose and was monitored for vaccine breakthrough infections in the following six months. The trial is registered on ClinicalTrials.gov (NCT04527614). Findings All included residents (n=85) and staff members (n=88) were SARS-CoV-2 infection naïve at third dose administration. Historical blood samples from 28 days post second dose were available from 42 residents and 42 staff members. Magnitude and quality of humoral and cellular immune responses were strongly boosted in residents post third compared to post second dose. Increases were less pronounced in staff members than in residents. At 28 days post third dose, differences between residents and staff had become mostly insignificant. Humoral, but not cellular, responses induced by a third dose were predictive of subsequent incidence of vaccine breakthrough infection in the six months following vaccination. Interpretation These data show that a third dose of mRNA COVID-19 vaccine largely closes the gap in humoral and cellular immune response observed after primary vaccination between NH residents and staff members but suggest that further boosting might be needed to achieve optimal protection against variants of concern in this vulnerable population group.
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26
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Oyebanji OA, Mylonakis E, Canaday DH. Vaccines for the Prevention of Coronavirus Disease 2019 in Older Adults. Infect Dis Clin North Am 2023; 37:27-45. [PMID: 36805013 PMCID: PMC9633624 DOI: 10.1016/j.idc.2022.11.002] [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] [Indexed: 11/06/2022]
Abstract
Institutionalized and community-dwelling older adults have been greatly impacted by the coronavirus disease 2019 (COVID-19) pandemic with increased morbidity and mortality. The advent of vaccines and their widespread use in this population has brought about a dramatic turnaround in COVID-19 outcomes. The immunogenicity and effectiveness of the various vaccine options worldwide are discussed. Optimization of vaccine usage will still be important to maximize protection due to reduced initial immunity, development of variant strains, and fading of immunity over time. There are also lessons learned specific to older populations for future pandemics of novel pathogens.
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Affiliation(s)
- Oladayo A Oyebanji
- Case Western Reserve University, School of Medicine, 10900 Euclid Ave, BRB 1025, Cleveland, OH 44106-4984, USA
| | - Eleftherios Mylonakis
- Infectious Diseases Division, The Miriam Hospital and Rhode Island Hospital, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, POB, 3rd Floor, Suite 328/330, Providence, RI 02903, USA
| | - David H Canaday
- Case Western Reserve University, School of Medicine, 10900 Euclid Ave, BRB 1025, Cleveland, OH 44106-4984, USA; Geriatric Research, Education and Clinical Center, Cleveland Veterans Affairs Medical Center, 10900 Euclid Ave, BRB 1025, Cleveland, OH 44106-4984, USA.
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27
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Itamochi M, Yazawa S, Inasaki N, Saga Y, Yamazaki E, Shimada T, Tamura K, Maenishi E, Isobe J, Nakamura M, Takaoka M, Sasajima H, Kawashiri C, Tani H, Oishi K. Neutralization of Omicron subvariants BA.1 and BA.5 by a booster dose of COVID-19 mRNA vaccine in a Japanese nursing home cohort. Vaccine 2023; 41:2234-2242. [PMID: 36858871 PMCID: PMC9968608 DOI: 10.1016/j.vaccine.2023.02.068] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 02/21/2023] [Accepted: 02/22/2023] [Indexed: 02/28/2023]
Abstract
The sustained epidemic of Omicron subvariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide concern, and older adults are at high risk. We conducted a prospective cohort study to assess the immunogenicity of COVID-19 mRNA vaccines (BNT162b2 or mRNA-1273) in nursing home residents and staff between May 2021 and December 2022. A total of 335 SARS-CoV-2 naïve individuals, including 141 residents (median age: 88 years) and 194 staff (median age: 44 years) participated. Receptor-binding domain (RBD) and nucleocapsid (N) protein IgG and neutralizing titer (NT) against the Wuhan strain, Alpha and Delta variants, and Omicron BA.1 and BA.5 subvariants were measured in serum samples drawn from participants after the second and third doses of mRNA vaccine using SARS-CoV-2 pseudotyped virus. Breakthrough infection (BTI) was confirmed by a notification of COVID-19 or a positive anti-N IgG result in serum after mRNA vaccination. Fifty-one participants experienced SARS-CoV-2 BTI during the study period. The RBD IgG and NTs against Omicron BA.1 and BA.5 were markedly increased in SARS CoV-2 naïve participants 2 months after the third dose of mRNA vaccine, compared to those 5 months after the second dose, and declined 5 months after the third dose. The decline in RBD IgG and NT against Omicron BA.1 and BA.5 in SARS-CoV-2 naïve participants after the second and the third dose was particularly marked in those aged ≥ 80 years. BTIs during the BA.5 epidemic period, which occurred between 2 and 5 months after the third dose, induced a robust NT against BA.5 even five months after the booster dose vaccination. Further studies are required to assess the sustainability of NTs elicited by Omicron-containing bivalent mRNA booster vaccine in older adults.
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Affiliation(s)
- Masae Itamochi
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Shunsuke Yazawa
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Noriko Inasaki
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Yumiko Saga
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Emiko Yamazaki
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Takahisa Shimada
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Kosuke Tamura
- Department of Research Planning, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Emi Maenishi
- Department of Bacteriology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Junko Isobe
- Department of Bacteriology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Masahiko Nakamura
- Department of Bacteriology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Misuzu Takaoka
- Department of Research Planning, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Hitoshi Sasajima
- Department of Research Planning, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Chikako Kawashiri
- Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Hideki Tani
- Department of Virology, Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan
| | - Kazunori Oishi
- Toyama Institute of Health, 17-1 Nakataikoyama, Imizu, Toyama 939-0363, Japan.
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28
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Freeman ML, Oyebanji OA, Moisi D, Payne M, Sheehan ML, Balazs AB, Bosch J, King CL, Gravenstein S, Lederman MM, Canaday DH. Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nursing Home Residents and Healthcare Workers. Open Forum Infect Dis 2023; 10:ofad063. [PMID: 36861088 PMCID: PMC9969739 DOI: 10.1093/ofid/ofad063] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 01/25/2023] [Indexed: 02/09/2023] Open
Abstract
Background Latent cytomegalovirus (CMV) infection is immunomodulatory and could affect mRNA vaccine responsiveness. We sought to determine the association of CMV serostatus and prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with antibody (Ab) titers after primary and booster BNT162b2 mRNA vaccinations in healthcare workers (HCWs) and nursing home (NH) residents. Methods Nursing home residents (N = 143) and HCWs (N = 107) were vaccinated and serological responses monitored by serum neutralization activity against Wuhan and Omicron (BA.1) strain spike proteins, and by bead-multiplex immunoglobulin G immunoassay to Wuhan spike protein and its receptor-binding domain (RBD). Cytomegalovirus serology and levels of inflammatory biomarkers were also measured. Results Severe acute respiratory syndrome coronavirus 2-naive CMV seropositive (CMV+) HCWs had significantly reduced Wuhan-neutralizing Ab (P = .013), anti-spike (P = .017), and anti-RBD (P = .011) responses 2 weeks after primary vaccination series compared with responses among CMV seronegative (CMV-) HCWs, adjusting for age, sex, and race. Among NH residents without prior SARS-CoV-2 infection, Wuhan-neutralizing Ab titers were similar 2 weeks after primary series but were reduced 6 months later (P = .012) between CMV+ and CMV- subjects. Wuhan-neutralizing Ab titers from CMV+ NH residents who had prior SARS-CoV-2 infection consistently trended lower than titers from SARS-CoV-2 experienced CMV- donors. These impaired Ab responses in CMV+ versus CMV- individuals were not observed after booster vaccination or with prior SARS-CoV-2 infection. Conclusions Latent CMV infection adversely affects vaccine-induced responsiveness to SARS-CoV-2 spike protein, a neoantigen not previously encountered, in both HCWs and NH residents. Multiple antigenic challenges may be required for optimal mRNA vaccine immunogenicity in CMV+ adults.
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Affiliation(s)
- Michael L Freeman
- Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Oladayo A Oyebanji
- Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Daniela Moisi
- Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Michael Payne
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
| | - Maegan L Sheehan
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA
| | | | - Jürgen Bosch
- Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, Rhode Island, USA
| | - Christopher L King
- Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
| | - Stefan Gravenstein
- Department of Health Services, Policy, and Practice, Brown University School of Public Health, Providence, Rhode Island, USA
- Center on Innovation in Long-Term Services and Supports, Providence Veterans Administration Medical Center, Providence, Rhode Island, USA
- Division of Geriatrics and Palliative Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Michael M Lederman
- Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - David H Canaday
- Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
- Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Cleveland, Ohio, USA
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Canaday DH, Oyebanji OA, White EM, Bosch J, Nugent C, Vishnepolskiy I, Abul Y, Didion EM, Paxitzis A, Sundheimer N, Ragavapuram V, Wilk D, Keresztesy D, Cao Y, St. Denis K, McConeghy KW, McDonald LC, Jernigan JA, Mylonakis E, Wilson BM, King CL, Balazs AB, Gravenstein S. SARS-CoV-2 Antibody Responses to the Ancestral SARS-CoV-2 Strain and Omicron BA.1 and BA.4/BA.5 Variants in Nursing Home Residents After Receipt of Bivalent COVID-19 Vaccine - Ohio and Rhode Island, September-November 2022. MMWR. MORBIDITY AND MORTALITY WEEKLY REPORT 2023; 72:100-106. [PMID: 36701254 PMCID: PMC9925133 DOI: 10.15585/mmwr.mm7204a4] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the period of Omicron variant predominance led to recommendations for booster doses with bivalent COVID-19 mRNA vaccines that include an Omicron BA.4/BA.5 spike protein component to broaden immune response and improve vaccine effectiveness against circulating Omicron variants (2). Recent studies suggest that bivalent booster doses provide substantial additional protection against SARS-CoV-2 infection and severe COVID-19-associated disease among immunocompetent adults who previously received only monovalent vaccines (3).* The immunologic response after receipt of bivalent boosters among nursing home residents, who often mount poor immunologic responses to vaccines, remains unknown. Serial testing of anti-spike protein antibody binding and neutralizing antibody titers in serum collected from 233 long-stay nursing home residents from the time of their primary vaccination series and including any subsequent booster doses, including the bivalent vaccine, was performed. The bivalent COVID-19 mRNA vaccine substantially increased anti-spike and neutralizing antibody titers against Omicron sublineages, including BA.1 and BA.4/BA.5, irrespective of previous SARS-CoV-2 infection or previous receipt of 1 or 2 booster doses. These data, in combination with evidence of low uptake of bivalent booster vaccination among residents and staff members in nursing homes (4), support the recommendation that nursing home residents and staff members receive a bivalent COVID-19 booster dose to reduce associated morbidity and mortality (2).
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Nugent C, Abul Y, White E, Shehadeh F, Kaczynski M, Felix LO, Ganesan N, Oyebanji OA, Vishnepolskiy I, Didion EM, Paxitzis A, Sheehan ML, Mylonakis E, Wilson BM, Balazs AB, Chan PA, King CL, Pfeifer WM, Dickerson E, Canaday DH, Gravenstein S. Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.01.22.23284881. [PMID: 36747765 PMCID: PMC9901038 DOI: 10.1101/2023.01.22.23284881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
We examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up to date on recommended SARS-CoV-2 vaccine booster doses.
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Milota T, Smetanova J, Skotnicova A, Rataj M, Lastovicka J, Zelena H, Parackova Z, Fejtkova M, Kanderova V, Fronkova E, Rejlova K, Sediva A, Kalina T. Clinical Outcomes, Immunogenicity, and Safety of BNT162b2 Vaccine in Primary Antibody Deficiency. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2023; 11:306-314.e2. [PMID: 36379409 DOI: 10.1016/j.jaip.2022.10.046] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 10/21/2022] [Accepted: 10/26/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Common variable immunodeficiency (CVID) is characterized by an impaired postvaccination response, high susceptibility to respiratory tract infections, and a broad spectrum of noninfectious complications. Thus, patients with CVID may be at high risk for COVID-19, and vaccination's role in prevention is questionable. OBJECTIVE We evaluated the clinical outcomes, safety, and dynamics of humoral and T-cell immune responses induced by the mRNA vaccine BNT162b2 in CVID. METHODS This prospective observational cohort study focused on the clinical outcomes (proportion of infected patients and disease severity), safety (incidences of adverse events and changes in laboratory parameters), and dynamics of humoral (specific postvaccination and virus-neutralizing antibody assessment) and T-cell immune responses (anti-SARS-CoV-2-specific T-cell detection) in 21 patients with CVID after a two-dose administration of BNT162b2. The patients were observed for 6 months. RESULTS Humoral response was observed in 52% of patients (11 of 21) at month 1 after vaccination but continuously decreased to 33.3% at month 6 (five of 15). Nevertheless, they had a remarkably lower anti-SARS-CoV-2 neutralizing antibody titer compared with healthy controls. The T-cell response was measurable in 46% of patients with CVID (six of 13) at month 1 and persisted over the study period. Mild infection occurred in three patients within the follow-up period (14.3%). The vaccine also exhibited a favorable safety profile. CONCLUSIONS The BNT162b2 vaccine elicited a measurable antibody response in a high proportion of patients, but it was limited by low titer of virus-neutralizing antibodies and rapid waning of anti-receptor-binding domain SARS-CoV-2-specific antibodies. T-cell response was detected in one-third of patients and remained stable within the follow-up period. Vaccination has favorable safety and clinical-related outcomes in preventing severe COVID-19.
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Affiliation(s)
- Tomas Milota
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic.
| | - Jitka Smetanova
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Aneta Skotnicova
- Childhood Leukemia Investigation Prague, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Michal Rataj
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Jan Lastovicka
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Hana Zelena
- Department of Virology, Public Health Institute, Ostrava, Czech Republic
| | - Zuzana Parackova
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Martina Fejtkova
- Childhood Leukemia Investigation Prague, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Veronika Kanderova
- Childhood Leukemia Investigation Prague, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Eva Fronkova
- Childhood Leukemia Investigation Prague, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Katerina Rejlova
- Childhood Leukemia Investigation Prague, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Anna Sediva
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
| | - Tomas Kalina
- Childhood Leukemia Investigation Prague, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czech Republic
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Immune Response and Effects of COVID-19 Vaccination in Patients with Lung Cancer-COVID Lung Vaccine Study. Cancers (Basel) 2022; 15:cancers15010137. [PMID: 36612134 PMCID: PMC9817972 DOI: 10.3390/cancers15010137] [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] [Received: 12/06/2022] [Revised: 12/16/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
Lung cancer patients represent a subgroup of special vulnerability in whom the SARS-CoV-2 infection could attain higher rates of morbidity and mortality. Therefore, those patients were recommended to receive SARS-CoV-2 vaccines once they were approved. However, little was known at that time regarding the degree of immunity developed after vaccination or vaccine-related adverse events, and more uncertainty involved the real need for a third dose. We sought to evaluate the immune response developed after vaccination, as well as the safety and efficacy of SARS-CoV-2 vaccines in a cohort of patients with lung cancer. Patients were identified through the Oncology/Hematology Outpatient Vaccination Program. Anti-Spike IgG was measured before any vaccine and at 3-6-, 6-9- and 12-15-month time points after the 2nd dose. Detailed clinical data were also collected. In total, 126 patients with lung cancer participated and received at least one dose of the SARS-CoV-2 vaccine. At 3-6 months after 2nd dose, 99.1% of baseline seronegative patients seroconverted and anti-Spike IgG titers went from a median value of 9.45 to 720 UI/mL. At the 6-9-month time point, titers raised to a median value of 924 UI/mL, and at 12-15 months, after the boost dose, they reached a median value of 3064 UI/mL. Adverse events to the vaccine were mild, and no SARS- CoV-2 infection-related deaths were recorded. In this lung cancer cohort, COVID-19 vaccines were safe and effective irrespective of the systemic anticancer therapy. Most of the patients developed anti-Spike IgG after the second dose, and these titers were maintained over time with low infection and reinfection rates with a mild clinical course.
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Sinha S, Konetzka RT. Association of COVID-19 Vaccination Rates of Staff and COVID-19 Illness and Death Among Residents and Staff in US Nursing Homes. JAMA Netw Open 2022; 5:e2249002. [PMID: 36580329 PMCID: PMC9856799 DOI: 10.1001/jamanetworkopen.2022.49002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
IMPORTANCE It is important to understand the association between staff vaccination rates and adverse COVID-19 outcomes in nursing homes. OBJECTIVE To assess the extent to which staff vaccination was associated with preventing COVID-19 cases and deaths among residents and staff in nursing homes. DESIGN, SETTING, AND PARTICIPANTS This longitudinal cohort study used data on COVID-19 outcomes in Medicare- and Medicaid-certified nursing homes in the US between May 30, 2021, and January 30, 2022. Participants included the residents of 15 042 US nursing homes that reported COVID-19 data to the Centers for Disease Control and Prevention and passed Centers for Medicare & Medicaid Services data quality checks in the National Healthcare Safety Network. EXPOSURES Weekly staff vaccination rates. MAIN OUTCOMES AND MEASURES Main outcomes are weekly COVID-19 cases and deaths among residents and weekly COVID-19 cases among staff. The treatment variable is the primary 2-dose staff vaccination rate in each facility each week. RESULTS In the primary analysis of 15 042 nursing homes before the Omicron variant wave (May 30 to December 5, 2021) using fixed effects of facility and week, increasing weekly staff vaccination rates by 10 percentage points was associated with 0.13 (95% CI, -0.20 to -0.10) fewer weekly COVID-19 cases per 1000 residents, 0.02 (95% CI, -0.03 to -0.01) fewer weekly COVID-19 deaths per 1000 residents, and 0.03 (95% CI, -0.04 to -0.02) fewer weekly COVID-19 staff cases. In the secondary analysis of the Omicron wave (December 5, 2021, to January 30, 2022), increasing staff vaccination rates were not associated with lower rates of adverse COVID-19 outcomes in nursing homes. CONCLUSIONS AND RELEVANCE The findings of this cohort study suggest that before the Omicron variant wave, increasing staff vaccination rates was associated with lower incidence of COVID-19 cases and deaths among residents and staff in US nursing homes. However, as newer, more infectious and transmissible variants of the virus emerged, the original 2-dose regimen of the COVID-19 vaccine as recommended in December 2020 was no longer associated with lower rates of adverse COVID-19 outcomes in nursing homes. Policy makers may want to consider longer-term policy options to increase the uptake of booster doses among staff in nursing homes.
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Affiliation(s)
- Soham Sinha
- Department of Public Health Sciences, Biological Sciences Division, University of Chicago, Chicago, Illinois
| | - R. Tamara Konetzka
- Department of Public Health Sciences, Biological Sciences Division, University of Chicago, Chicago, Illinois
- Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, Illinois
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Primary SARS-CoV-2 Infections, Re-infections and Vaccine Effectiveness during the Omicron Transmission Period in Healthcare Workers of Trieste and Gorizia (Northeast Italy), 1 December 2021-31 May 2022. Viruses 2022; 14:v14122688. [PMID: 36560692 PMCID: PMC9784665 DOI: 10.3390/v14122688] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/23/2022] [Accepted: 11/24/2022] [Indexed: 12/03/2022] Open
Abstract
Objective: To evaluate the incidence of primary and recurrent COVID-19 infections in healthcare workers (HCWs) routinely screened for SARS-CoV-2 by nasopharyngeal swabs during the Omicron wave. Design: Dynamic Cohort study of HCWs (N = 7723) of the University Health Agency Giuliano Isontina (ASUGI), covering health services of the provinces of Trieste and Gorizia (Northeast Italy). Cox proportional hazard model was employed to estimate the risk of primary as well as recurrent SARS-CoV-2 infection from 1 December 2021 through 31 May 2022, adjusting for a number of confounding factors. Results: By 1 December 2021, 46.8% HCWs of ASUGI had received the booster, 37.2% were immunized only with two doses of COVID-19 vaccines, 6.0% only with one dose and 10.0% were unvaccinated. During 1 March 2020-31 May 2022, 3571 primary against 406 SARS-CoV-2 recurrent infections were counted among HCWs of ASUGI, 59.7% (=2130/3571) versus 95.1% (=386/406) of which occurring from 1 December 2021 through 31 May 2022, respectively. All HCWs infected by SARS-CoV-2 during 1 December 2021 through 31 May 2022 presented mild flu-like disease. Compared to staff working in administrative services, the risk of primary as well as recurrent SARS-CoV-2 infection increased in HCWs with patient-facing clinical tasks (especially nurses and other categories of HCWs) and in all clinical wards but COVID-19 units and community health services. Regardless of the number of swab tests performed during the study period, primary infections were less likely in HCWs immunized with one dose of COVID-19 vaccine. By contrast, the risk of SARS-CoV-2 re-infection was significantly lower in HCWs immunized with three doses (aHR = 0.58; 95%CI: 0.41; 0.80). During the study period, vaccine effectiveness (VE = 1-aHR) of the booster dose declined to 42% against re-infections, vanishing against primary SARS-CoV-2 infections. Conclusions: Though generally mild, SARS-CoV-2 infections and re-infections surged during the Omicron transmission period. Compared to unvaccinated colleagues, the risk of primary SARS-CoV-2 infection was significantly lower in HCWs immunized just with one dose of COVID-19 vaccines. By Italian law, HCWs immunized only with one dose were either suspended or re-assigned to job tasks not entailing patient facing contact; hence, while sharing the same biological risk of unvaccinated colleagues, they arguably had a higher level of protection against COVID-19 infection. By contrast, SARS-CoV-2 re-infections were less likely in HCWs vaccinated with three doses, suggesting that hybrid humoral immunity by vaccination combined with natural infection provided a higher level of protection than vaccination only. In this stage of the pandemic, where SARS-CoV-2 is more infectious yet much less pathogenic, health protection measures in healthcare premises at higher biological risk seem the rational approach to control the transmission of the virus.
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Smetanova J, Milota T, Rataj M, Hurnakova J, Zelena H, Horvath R. SARS-CoV-2-specific humoral and cellular immune responses to BNT162b2 vaccine in Fibrodysplasia ossificans progressiva patients. Front Immunol 2022; 13:1017232. [PMID: 36439163 PMCID: PMC9682080 DOI: 10.3389/fimmu.2022.1017232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 10/24/2022] [Indexed: 11/11/2022] Open
Abstract
Introduction Fibrodysplasia ossificans progressiva (FOP) is characterized by progressive heterotopic ossification triggered by various conditions, such as trauma, infection, including COVID-19 infection, and vaccination. Although SARS-CoV-2 vaccinations prevent poor outcomes in the general population, there is limited evidence on safety, immunogenicity, and efficacy of SARS-CoV-2 vaccines for inpatients with FOP. Methods A case series of two patients with FOP focused on humoral, cellular post-vaccination response, and the incidence of adverse events after administration of the BNT162b2 vaccine (Comirnaty). Results Injection site reactions, fever, myalgia, and fatigue were the most common adverse events (AE). Neither severe AE (SAE), nor disease flare-ups were observed. No differences between patients with FOP and healthy controls were observed in humoral and cellular responses. Conclusions The BNT162b2 vaccine induced high humoral and cellular response levels in patients with FOP. Vaccination was not associated with SAE or disease relapse. The AEs spectrum was comparable to that of the general population.
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Affiliation(s)
- Jitka Smetanova
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czechia
| | - Tomas Milota
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czechia
- *Correspondence: Tomas Milota,
| | - Michal Rataj
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czechia
| | - Jana Hurnakova
- Department of Paediatric and Adult Rheumatology, Motol University Hospital, Prague, Czechia
| | - Hana Zelena
- Department of Virology, Public Health Institute, Ostrava, Czechia
| | - Rudolf Horvath
- Department of Immunology, Second Faculty of Medicine Charles University and Motol University Hospital, Prague, Czechia
- Department of Paediatric and Adult Rheumatology, Motol University Hospital, Prague, Czechia
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Jacobsen H, Katzmarzyk M, Higdon MM, Jiménez VC, Sitaras I, Bar-Zeev N, Knoll MD. Post-Vaccination Neutralization Responses to Omicron Sub-Variants. Vaccines (Basel) 2022; 10:1757. [PMID: 36298622 PMCID: PMC9607453 DOI: 10.3390/vaccines10101757] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/05/2022] [Accepted: 10/12/2022] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND The emergence of the Omicron variant (B.1.1.529), which correlated with dramatic losses in cross-neutralization capacity of post-vaccination sera, raised concerns about the effectiveness of COVID-19 vaccines against infection and disease. Several clinically relevant sub-variants subsequently emerged rapidly. METHODS We evaluated published and pre-print studies reporting sub-variant specific reductions in cross-neutralization compared to the prototype strain of SARS-CoV-2 and between sub-variants. Median fold-reduction across studies was calculated by sub-variant and vaccine platform. RESULTS Among 178 studies with post-vaccination data, after primary vaccination the sub-variant specific fold-reduction in neutralization capacity compared to the prototype antigen varied widely, from median 4.2-fold for BA.3 to 40.1-fold for BA.2.75; in boosted participants fold-reduction was similar for most sub-variants (5.3-fold to 7.0-fold); however, a more pronounced fold-change was observed for sub-variants related to BA.4 and BA.5 (10.4-fold to 14.2-fold). Relative to BA.1, the other Omicron sub-variants had similar neutralization capacity post-primary vaccination (range median 0.8-fold to 1.1-fold) and post-booster (0.9-fold to 1.4-fold) except for BA.4/5-related sub-variants which was higher (2.1-fold to 2.7-fold). Omicron sub-variant-specific responder rates were low post-primary vaccination (range median 28.0% to 65.9%) compared to the prototype (median 100%) but improved post-booster (range median 73.3% to 100%). CONCLUSIONS Fold-reductions in neutralization titers were comparable post-booster except for sub-variants related to BA.4 and BA.5, which had higher fold-reduction. Assessment after primary vaccination was not possible because of overall poor neutralization responses causing extreme heterogeneity. Considering large fold-decreases in neutralization titers relative to the parental strain for all Omicron sub-variants, vaccine effectiveness is very likely to be reduced against all Omicron sub-variants, and probably more so against variants related to BA.4 or BA.5.
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Affiliation(s)
- Henning Jacobsen
- Department of Viral Immunology, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany
| | - Maeva Katzmarzyk
- Department of Viral Immunology, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany
| | - Melissa M. Higdon
- International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | | | - Ioannis Sitaras
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Naor Bar-Zeev
- International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Maria Deloria Knoll
- International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
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Abdelmoneim SA, Sallam M, Hafez DM, Elrewany E, Mousli HM, Hammad EM, Elkhadry SW, Adam MF, Ghobashy AA, Naguib M, Nour El-Deen AES, Aji N, Ghazy RM. COVID-19 Vaccine Booster Dose Acceptance: Systematic Review and Meta-Analysis. Trop Med Infect Dis 2022; 7:298. [PMID: 36288039 PMCID: PMC9611447 DOI: 10.3390/tropicalmed7100298] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/03/2022] [Accepted: 10/04/2022] [Indexed: 11/17/2022] Open
Abstract
The World Health Organization (WHO) recommended coronavirus disease 2019 (COVID-19) booster dose vaccination after completing the primary vaccination series for individuals ≥18 years and most-at-risk populations. This study aimed to estimate the pooled proportion of COVID-19 vaccine booster dose uptake and intention to get the booster dose among general populations and healthcare workers (HCWs). We searched PsycINFO, Scopus, EBSCO, MEDLINE Central/PubMed, ProQuest, SciELO, SAGE, Web of Science, Google Scholar, and ScienceDirect according to PRISMA guidelines. From a total of 1079 screened records, 50 studies were extracted. Meta-analysis was conducted using 48 high-quality studies according to the Newcastle-Ottawa Scale quality assessment tool. Using the 48 included studies, the pooled proportion of COVID-19 vaccine booster dose acceptance among 198,831 subjects was 81% (95% confidence interval (CI): 75-85%, I2 = 100%). The actual uptake of the booster dose in eight studies involving 12,995 subjects was 31% (95% CI: 19-46%, I2 = 100%), while the intention to have the booster dose of the vaccine was 79% (95% CI: 72-85%, I2 = 100%). The acceptance of the booster dose of COVID-19 vaccines among HCWs was 66% (95% CI: 58-74%), I2 = 99%). Meta-regression revealed that previous COVID-19 infection was associated with a lower intention to have the booster dose. Conversely, previous COVID-19 infection was associated with a significantly higher level of booster dose actual uptake. The pooled booster dose acceptance in the WHO region of the Americas, which did not include any actual vaccination, was 77% (95% CI: 66-85%, I2 = 100%). The pooled acceptance of the booster dose in the Western Pacific was 89% (95% CI: 84-92%, I2 = 100), followed by the European region: 86% (95% CI: 81-90%, I2 = 99%), the Eastern Mediterranean region: 59% (95% CI: 46-71%, I2 = 99%), and the Southeast Asian region: 52% (95% CI: 43-61%, I2 = 95). Having chronic disease and trust in the vaccine effectiveness were the significant predictors of booster dose COVID-19 vaccine acceptance. The global acceptance rate of COVID-19 booster vaccine is high, but the rates vary by region. To achieve herd immunity for the disease, a high level of vaccination acceptance is required. Intensive vaccination campaigns and programs are still needed around the world to raise public awareness regarding the importance of accepting COVID-19 vaccines needed for proper control of the pandemic.
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Affiliation(s)
- Shaimaa Abdelaziz Abdelmoneim
- Clinical Research Administration, Alexandria Directorate of Health Affairs, Egyptian Ministry of Health and Population, Alexandria 21554, Egypt
| | - Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
| | - Dina Mohamed Hafez
- Pharmacy Department, Alexandria University Students Hospital, Alexandria 5422023, Egypt
| | - Ehab Elrewany
- Tropical Health Department, High Institute of Public Health, Alexandria University, Alexandria 21561, Egypt
| | - Hesham Metwalli Mousli
- Continuous Quality Improvement & Patient Safety Department, Alexandria Urology Hospital, Alexandria 5442045, Egypt
| | | | - Sally Waheed Elkhadry
- Department of Epidemiology and Preventive Medicine, National Liver Institute, Menoufia University, Menoufia 32511, Egypt
| | | | | | - Manal Naguib
- Egyptian Ministry of Health and Population, Alexandria 21554, Egypt
| | | | - Narjiss Aji
- Faculty of Medicine and Pharmacy of Rabat, Mohammed V University, Rabat 10100, Morocco
| | - Ramy Mohamed Ghazy
- Tropical Health Department, High Institute of Public Health, Alexandria University, Alexandria 21561, Egypt
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Streibl BI, Lahne H, Grahl A, Agsten P, Bichler M, Büchl C, Damzog M, Eberle U, Gärtner S, Hobmaier B, Margos G, Hoch M, Jungnick S, Jonas W, Katz K, Laubert L, Schutt B, Seidl C, Treis B, Weindl D, Zilch K, Wildner M, Liebl B, Ackermann N, Sing A, Fingerle V. Epidemiological and Serological Analysis of a SARS-CoV-2 Outbreak in a Nursing Home: Impact of SARS-CoV-2 Vaccination and Enhanced Neutralizing Immunity Following Breakthrough Infection. Microorganisms 2022; 10:microorganisms10091809. [PMID: 36144413 PMCID: PMC9505589 DOI: 10.3390/microorganisms10091809] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 08/28/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Despite a vaccination rate of 82.0% (n = 123/150), a SARS-CoV-2 (Alpha) outbreak with 64.7% (n = 97/150) confirmed infections occurred in a nursing home in Bavaria, Germany. Objective: the aim of this retrospective cohort study was to examine the effects of the Corminaty vaccine in a real-life outbreak situation and to obtain insights into the antibody response to both vaccination and breakthrough infection. Methods: the antibody status of 106 fully vaccinated individuals (54/106 breakthrough infections) and epidemiological data on all 150 residents and facility staff were evaluated. Results: SARS-CoV-2 infections (positive RT-qPCR) were detected in 56.9% (n = 70/123) of fully vaccinated, compared to 100% (n = 27/27) of incompletely or non-vaccinated individuals. The proportion of hospitalized and deceased was 4.1% (n = 5/123) among fully vaccinated and therewith lower compared to 18.5% (n = 5/27) hospitalized and 11.1% (n = 3/27) deceased among incompletely or non-vaccinated. Ct values were significantly lower in incompletely or non-vaccinated (p = 0.02). Neutralizing antibodies were detected in 99.1% (n = 105/106) of serum samples with significantly higher values (p < 0.001) being measured post-breakthrough infection. α-N-antibodies were detected in 37.7% of PCR positive but not in PCR negative individuals. Conclusion: Altogether, our data indicate that SARS-CoV-2 vaccination does provide protection against infection, severe disease progression and death with regards to the Alpha variant. Nonetheless, it also shows that infection and transmission are possible despite full vaccination. It further indicates that breakthrough infections can significantly enhance α-S- and neutralizing antibody responses, indicating a possible benefit from booster vaccinations.
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Affiliation(s)
- Barbara I. Streibl
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
- Correspondence: (B.I.S.); (V.F.)
| | - Heidi Lahne
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Andreas Grahl
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Philipp Agsten
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Magdalena Bichler
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | | | | | - Ute Eberle
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | | | - Bernhard Hobmaier
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Gabriele Margos
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Martin Hoch
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Sabrina Jungnick
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Walter Jonas
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Katharina Katz
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | | | | | - Cornelia Seidl
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Bianca Treis
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Daniel Weindl
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Karen Zilch
- Health Office Neumarkt, 92318 Neumarkt, Germany
| | - Manfred Wildner
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Bernhard Liebl
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Nikolaus Ackermann
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Andreas Sing
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
| | - Volker Fingerle
- Public Health Microbiology Unit, Bavarian Health and Food Safety Authority, 85764 Oberschleißheim, Germany
- Correspondence: (B.I.S.); (V.F.)
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Yang L, Van Beek M, Wang Z, Muecksch F, Canis M, Hatziioannou T, Bieniasz PD, Nussenzweig MC, Chakraborty AK. Antigen presentation dynamics shape the response to emergent variants like SARS-CoV-2 Omicron strain after multiple vaccinations with wild type strain. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2022:2022.08.24.505127. [PMID: 36052368 PMCID: PMC9435403 DOI: 10.1101/2022.08.24.505127] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The Omicron variant of SARS-CoV-2 evades neutralization by most serum antibodies elicited by two doses of mRNA vaccines, but a third dose of the same vaccine increases anti-Omicron neutralizing antibodies. By combining computational modeling with data from vaccinated humans we reveal mechanisms underlying this observation. After the first dose, limited antigen availability in germinal centers results in a response dominated by B cells with high germline affinities for immunodominant epitopes that are significantly mutated in an Omicron-like variant. After the second dose, expansion of these memory cells and differentiation into plasma cells shape antibody responses that are thus ineffective for such variants. However, in secondary germinal centers, pre-existing higher affinity antibodies mediate enhanced antigen presentation and they can also partially mask dominant epitopes. These effects generate memory B cells that target subdominant epitopes that are less mutated in Omicron. The third dose expands these cells and boosts anti-variant neutralizing antibodies.
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Affiliation(s)
- Leerang Yang
- Departments of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Matthew Van Beek
- Departments of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Zijun Wang
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
| | - Frauke Muecksch
- Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
| | - Marie Canis
- Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
| | | | - Paul D Bieniasz
- Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
- Howard Hughes Medical Institute
| | - Michel C Nussenzweig
- Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
- Howard Hughes Medical Institute
| | - Arup K Chakraborty
- Departments of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139
- Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139
- Institute for Medical Engineering & Science, Massachusetts Institute of Technology; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA 02139
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Chong Y, Goto T, Tani N, Yonekawa A, Ikematsu H, Shimono N, Tanaka Y, Akashi K. Pronounced antibody elevation after SARS-CoV-2 BNT162b2 mRNA booster vaccination in nursing home residents. Influenza Other Respir Viruses 2022; 16:1066-1071. [PMID: 35962568 PMCID: PMC9530588 DOI: 10.1111/irv.13030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 07/16/2022] [Accepted: 07/21/2022] [Indexed: 11/30/2022] Open
Abstract
Background Infection control during COVID‐19 outbreaks in nursing facilities is a critical public health issue. Antibody responses before and after the third (booster) dose of SARS‐CoV‐2 vaccination in nursing home residents have not been fully characterized. Methods This study included 117 individuals: 54 nursing home residents (mean age, 83.8 years; 39 SARS‐CoV‐2‐naive and 15 previously infected) and 63 healthcare workers (mean age, 45.8 years; 32 SARS‐CoV‐2‐naive and 31 previously infected). Anti‐spike (receptor‐binding domain [RBD]) and anti‐nucleocapsid antibody responses to BNT162b2 mRNA vaccination and their related factors were evaluated using pre‐ (shortly and 6 months after the second dose) and post‐booster vaccination samples. Results The median anti‐spike (RBD) IgG level in SARS‐CoV‐2‐naive residents 6 months after the second dose was the lowest among the four groups, with a decreasing rate of over 90%. The median rate of increase before and after the third dose in SARS‐CoV‐2‐naive residents was significantly higher than that in SARS‐CoV‐2‐naive healthcare workers (64.1‐ vs. 37.0‐fold, P = 0.003), with the highest level among the groups. The IgG ratio of SARS‐CoV‐2‐naive residents to healthcare workers after the second and third doses changed from one‐fifth (20%) to one‐half (50%). The rate of increase after the third dose in previously infected individuals was three‐ to fourfold, regardless of residents or healthcare workers. Conclusions Advanced aged nursing home residents, poor responders in the initial SARS‐CoV‐2 vaccine series, could obtain sufficient antibody responses with the additional booster dose, despite more than 6 months after the second.
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Affiliation(s)
- Yong Chong
- Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine), Fukuoka, Japan
| | - Takeyuki Goto
- Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine), Fukuoka, Japan
| | - Naoki Tani
- Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine), Fukuoka, Japan
| | - Akiko Yonekawa
- Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine), Fukuoka, Japan
| | | | - Nobuyuki Shimono
- Center for the Study of Global Infection, Kyushu University Hospital, Fukuoka, Japan
| | - Yosuke Tanaka
- Medical Corporation SOUSEIKAI, Kanenokuma Hospital, Fukuoka, Japan
| | - Koichi Akashi
- Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine), Fukuoka, Japan
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Zarębska-Michaluk D, Hu C, Brzdęk M, Flisiak R, Rzymski P. COVID-19 Vaccine Booster Strategies for Omicron SARS-CoV-2 Variant: Effectiveness and Future Prospects. Vaccines (Basel) 2022; 10:vaccines10081223. [PMID: 36016111 PMCID: PMC9412973 DOI: 10.3390/vaccines10081223] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/25/2022] [Accepted: 07/28/2022] [Indexed: 12/05/2022] Open
Abstract
In the light of the lack of authorized COVID-19 vaccines adapted to the Omicron variant lineage, the administration of the first and second booster dose is recommended. It remains important to monitor the efficacy of such an approach in order to inform future preventive strategies. The present paper summarizes the research progress on the effectiveness of the first and second booster doses of COVID-19. It also discusses the potential approach in vaccination strategies that could be undertaken to maintain high levels of protection during the waves of SARS-CoV-2 infections. Although this approach can be based, with some shortcomings, on the first-generation vaccines, other vaccination strategies should be explored, including developing multiple antigen-based (multivariant-adapted) booster doses with enhanced durability of immune protection, e.g., through optimization of the half-life of generated antibodies.
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Affiliation(s)
- Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Jan Kochanowski University, 25-369 Kielce, Poland; (D.Z.-M.); (M.B.)
| | - Chenlin Hu
- College of Pharmacy, University of Houston, Houston, TX 77204, USA;
| | - Michał Brzdęk
- Department of Infectious Diseases, Jan Kochanowski University, 25-369 Kielce, Poland; (D.Z.-M.); (M.B.)
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland;
| | - Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland
- Integrated Science Association (ISA), Universal Scientific Education and Research Network (USERN), 60-806 Poznań, Poland
- Correspondence:
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McGarry BE, Gandhi AD, Syme M, Berry SD, White EM, Grabowski DC. Association of State COVID-19 Vaccine Mandates With Staff Vaccination Coverage and Staffing Shortages in US Nursing Homes. JAMA HEALTH FORUM 2022; 3:e222363. [PMID: 35983581 PMCID: PMC9338409 DOI: 10.1001/jamahealthforum.2022.2363] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/08/2022] [Indexed: 11/14/2022] Open
Abstract
Importance Several states implemented COVID-19 vaccine mandates for nursing home employees, which may have improved vaccine coverage but may have had the unintended consequence of staff departures. Objective To assess whether state vaccine mandates for US nursing home employees are associated with staff vaccination rates and reported staff shortages. Design Setting and Participants This cohort study performed event study analyses using National Healthcare Safety Network data from June 6, 2021, through November 14, 2021. Changes in weekly staff vaccination rates and reported staffing shortages were evaluated for nursing homes in states with mandates after the mandate announcement compared with changes in facilities in nonmandate states. An interaction between the mandates and county political leaning was considered. Data analysis was performed from February to March 2022. Exposures Weeks after announcement of a state's COVID-19 vaccine mandate. Main Outcomes and Measures Weekly percentage of all health care staff at a nursing home who received at least 1 COVID-19 vaccine dose, and a weekly indicator of whether a nursing home reported a staffing shortage. Results Among 38 study-eligible states, 26 had no COVID-19 vaccine mandate for nursing home employees, 4 had a mandate with a test-out option, and 8 had a mandate with no test-out option. Ten weeks or more after mandate announcement, nursing homes in states with a mandate and no test-out option experienced a 6.9 percentage point (pp) increase in staff vaccination coverage (95% CI, -0.1 to 13.9); nursing homes in mandate states with a test-out option experienced a 3.1 pp increase (95% CI, 0.5 to 5.7) compared with facilities in nonmandate states. No significant increases were detected in the frequency of reported staffing shortages after a mandate announcement in mandate states with or without test-out options. Increases in vaccination rates in states with mandates were larger in Republican-leaning counties (14.3 pp if no test-out option; 4.3 pp with option), and there was no evidence of increased staffing shortages. Conclusions and Relevance The findings of this cohort study suggest that state-level vaccine mandates were associated with increased staff vaccination coverage without increases in reported staffing shortages. Vaccination increases were largest when mandates had no test-out option and were also larger in Republican-leaning counties, which had lower mean baseline vaccination rates. These findings support the use of state mandates for booster doses for nursing home employees because they may improve vaccine coverage, even in areas with greater vaccine hesitancy.
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Affiliation(s)
- Brian E. McGarry
- Division of Geriatrics and Aging, Department of Medicine, University of Rochester Medical Center, Rochester, New York
| | - Ashvin D. Gandhi
- Anderson School of Management, University of California Los Angeles
| | - Maggie Syme
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts
| | - Sarah D. Berry
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts
- Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts
| | - Elizabeth M. White
- Department of Health Services, Policy & Practice, Brown University School of Public Health, Providence, Rhode Island
| | - David C. Grabowski
- Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts
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