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Zhang Y, Wang S, Li G, Shi J, Chang X, Zhang H, Zhu F, Li J, Pan H, Sun J. Immunogenicity and safety of a live attenuated varicella vaccine in healthy subjects aged between 13 to 55 years: a double-blind, randomized, active-controlled phase III clinical trial in China. Expert Rev Vaccines 2025; 24:157-164. [PMID: 39916494 DOI: 10.1080/14760584.2025.2457463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 01/20/2025] [Indexed: 02/09/2025]
Abstract
BACKGROUND Adolescents and adults who contract chickenpox are at a higher risk of severe complications. Vaccination with the varicella vaccine (VarV) effectively prevents chickenpox. RESEARCH DESIGN AND METHODS In this phase III, single-center, randomized, double-blind, active-controlled trial, 1,200 healthy participants were randomly assigned in a 1:1 ratio to receive two doses of either the test vaccine or the active control vaccine. Varicella-zoster virus (VZV) antibody was detected before vaccination and 42 days after the two doses of vaccination. RESULTS The lower limits of the 95% CI for the differences in seroconversion rates and geometric mean titer (GMT) ratios between the two groups were greater than their respective pre-set non-inferiority margins. The overall incidence of Adverse events (AEs) and adverse reactions (ARs) in the test group was significantly lower than those in the control group. Additionally, the incidence rates of swelling and fatigue were lower in the test group compared to the control group after vaccination. CONCLUSIONS The test freeze-dried live attenuated VarV demonstrated good immunogenicity and higher safety compared to the active control vaccine in healthy participants aged 13-55 years. CLINICAL TRIALS REGISTRATION www.clinicaltrials.gov identifier: NCT06592456.
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Affiliation(s)
- Yang Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, PR China
- Department of Immunization Planning, Gaochun District Center for Disease Control and Prevention, Nanjing, PR China
| | - Shiyuan Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, PR China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, PR China
| | - Guifan Li
- Registration Department, Beijing Minhai Biotechnology Co.,Ltd., Beijing, China
| | - Jinhui Shi
- Registration Department, Beijing Minhai Biotechnology Co.,Ltd., Beijing, China
| | - Xianyun Chang
- Registration Department, Beijing Minhai Biotechnology Co.,Ltd., Beijing, China
| | - Hao Zhang
- Registration Department, Beijing Minhai Biotechnology Co.,Ltd., Beijing, China
| | - Fengcai Zhu
- Vaccine Clinical Evaluation Department, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China
| | - Jingxin Li
- Vaccine Clinical Evaluation Department, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China
| | - Hongxing Pan
- Vaccine Clinical Evaluation Department, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China
| | - Jinfang Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, PR China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, PR China
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Qui M, Hariharaputran S, Hang SK, Zhang J, Tan CW, Chong CY, Low J, Wang L, Bertoletti A, Yung CF, Le Bert N. T cell hybrid immunity against SARS-CoV-2 in children: a longitudinal study. EBioMedicine 2024; 105:105203. [PMID: 38896919 PMCID: PMC11237860 DOI: 10.1016/j.ebiom.2024.105203] [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: 01/26/2024] [Revised: 05/27/2024] [Accepted: 05/31/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children. METHODS We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining. FINDINGS After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens. INTERPRETATION Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19. FUNDING This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).
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Affiliation(s)
- Martin Qui
- Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
| | | | - Shou Kit Hang
- Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
| | - Jinyan Zhang
- Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
| | - Chee Wah Tan
- Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Chia Yin Chong
- KK Women's and Children's Hospital, Department of Paediatrics, Infectious Diseases Service, Singapore; Duke-NUS Medical School, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Jenny Low
- Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore; Singapore General Hospital, Department of Infectious Diseases, Singapore
| | - Linfa Wang
- Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore
| | - Antonio Bertoletti
- Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore; Singapore Immunology Network, A∗STAR, Singapore
| | - Chee Fu Yung
- KK Women's and Children's Hospital, Department of Paediatrics, Infectious Diseases Service, Singapore; Duke-NUS Medical School, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Nina Le Bert
- Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
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Arvin AM. Insights From Studies of the Genetics, Pathogenesis, and Immunogenicity of the Varicella Vaccine. J Infect Dis 2022; 226:S385-S391. [PMID: 36265853 DOI: 10.1093/infdis/jiac278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
While the varicella vaccine was created with approaches established for other live attenuated viral vaccines, novel methods to probe virus-host interactions have been used to explore the genetics, pathogenesis, and immunogenicity of the vaccine compared to wild-type varicella-zoster virus (VZV). As summarized here, a mechanism-based understanding of the safety and efficacy of the varicella vaccine has been achieved through these investigations.
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Affiliation(s)
- Ann M Arvin
- Departments of Pediatrics and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA
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4
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Shin D, Shin Y, Kim E, Nam H, Nan H, Lee J. Immunological characteristics of MAV/06 strain of varicella-zoster virus vaccine in an animal model. BMC Immunol 2022; 23:27. [PMID: 35658899 PMCID: PMC9166591 DOI: 10.1186/s12865-022-00503-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 04/28/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Varicella-zoster virus (VZV) is a pathogen that causes chickenpox and shingles in humans. Different types of the varicella vaccines derived from the Oka and MAV/06 strains are commercially available worldwide. Although the MAV/06 vaccine was introduced in 1990s, little was known about immunological characteristics. RESULTS Here, we evaluated B and T cell immune response in animals inoculated with the Oka and MAV/06 vaccines as well as a new formulation of the MAV/06 vaccine. A variety of test methods were applied to evaluate T and B cell immune response. Plaque reduction neutralization test (PRNT) and fluorescent antibody to membrane antigen (FAMA) assay were conducted to measure the MAV/06 vaccine-induced antibody activity against various VZVs. Glycoprotein enzyme-linked immunosorbent assay (gpELISA) was used to compare the degree of the antibody responses induced by the two available commercial VZV vaccines and the MAV/06 vaccine. Interferon-gamma enzyme-linked immunosorbent spot (IFN-γ ELISpot) assays and cytokine bead array (CBA) assays were conducted to investigate T cell immune responses. Antibodies induced by MAV/06 vaccination showed immunogenicity against a variety of varicella-zoster virus and cross-reactivity among the virus clades. CONCLUSIONS It is indicating the similarity of the antibody responses induced by commercial varicella vaccines and the MAV/06 vaccine. Moreover, VZV-specific T cell immune response from MAV/06 vaccination was increased via Th1 cell response. MAV/06 varicella vaccine induced both humoral and cellular immune response via Th1 cell mediated response.
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Affiliation(s)
- Duckhyang Shin
- GC Biopharma Corp., 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea
| | - Younchul Shin
- GC Biopharma Corp., 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea
| | - Eunmi Kim
- MOGAM Institute for Biomedical Research, 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea
| | - Hyojung Nam
- GC Biopharma Corp., 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea
| | - Haiyan Nan
- GC Biopharma Corp., 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea
| | - Jaewoo Lee
- GC Biopharma Corp., 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea.
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5
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Levin MJ, Weinberg A. Immune Responses to Varicella-Zoster Virus Vaccines. Curr Top Microbiol Immunol 2022; 438:223-246. [PMID: 35102438 DOI: 10.1007/82_2021_245] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The live attenuated varicella vaccine is intended to mimic the tempo and nature of the humoral and cell-mediated immune responses to varicella infection. To date, two doses of varicella vaccine administered in childhood have been very effective in generating varicella-zoster virus (VZV) immune responses that prevent natural infection for at least several decades. After primary infection, the infecting VZV establishes latency in sensory and cranial nerve ganglia with the potential to reactivate and cause herpes zoster. Although, the immune responses developed during varicella are important for preventing herpes zoster they wane with increasing age (immune senescence) or with the advent of immune suppression. Protection can be restored by increasing cell-mediated immune responses with two doses of an adjuvanted recombinant VZV glycoprotein E vaccine that stimulates both VZV-and gE-specific immunity. This vaccine provides ~85-90% protection against herpes zoster for 7-8 years (to date).
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Affiliation(s)
- Myron J Levin
- Departments of Pediatrics and Medicine, University of Colorado Denver School of Medicine, Anschutz Medical Campus, Aurora, CO, USA
| | - Adriana Weinberg
- Departments of Pediatrics, Medicine, and Pathology, University of Colorado Denver School of Medicine, Anschutz Medical Campus, Aurora, CO, USA.
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AbdelMassih A, El Shershaby M, Gaber H, Habib M, Gamal N, Husseiny R, AlShehry N, Amin A, Heikal B, El-Husseiny N, Moursi M, Ismail HA, Senoussy S, ElSharkawy R, AlZayat HA, ElMahdy G, Moawad H, Genena A, ElKiki A, Reda M, Khalil M, Al Ramady R, Radwan N, Khaled-Ibn-ElWalid M, Amin H, Hozaien R, Kamel A, Fouda R. Should we vaccinate the better seroconverters or the most vulnerable? Game changing insights for COVID-19 vaccine prioritization policies. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2021. [PMCID: PMC8637024 DOI: 10.1186/s43054-021-00086-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background With the rapid rise in COVID 19 cases incomparable to the number of vaccinations available, there has been a demand to prioritize the older age groups receiving the vaccine as they have more risk of morbidity and mortality and thus better outcome from vaccination. Main body Some studies showed a lower seroconversion rate in older group patients; thus, we discuss the necessity to reprioritize vaccinations to younger age groups who have better seroconversion rates, but we may face some ethical dilemma that could hinder our hypothesis. Decreased seroconversion rates in adults are attributable to immuno-senescence which involves a decrease in humoral and cellular-mediated immunity with age. Despite this fact, there remains some ethical dilemma that can hinder widespread vaccination of younger generations, the most important of which is the unknown long-term effects of COVID-19 vaccines due their fast-tracking under the pressure of the pandemic. Short conclusion Prioritizing children vaccination against COVID-19 seems an interesting strategy that can help in containing the pandemic. Resolving some ethical dilemma needs to be done before implementing such strategy.
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Indian Academy of Pediatrics (IAP) Advisory Committee on Vaccines and Immunization Practices (ACVIP): Recommended Immunization Schedule (2020-21) and Update on Immunization for Children Aged 0 Through 18 Years. Indian Pediatr 2021. [PMID: 33257602 PMCID: PMC7840391 DOI: 10.1007/s13312-021-2096-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Justification In view of new developments in vaccinology and the availability of new vaccines, there is a need to revise/review the existing immunization recommendations. Process Advisory Committee on Vaccines and Immunization Practices (ACVIP) of Indian Academy of Pediatrics (IAP) had a physical meeting in March, 2020 followed by online meetings (September-October, 2020), to discuss the updates and new recommendations. Opinion of each member was sought on the various recommendations and updates, following which an evidence-based consensus was reached. Objectives To review and revise the IAP recommendations for 2020–21 and issue recommendations on existing and new vaccines. Recommendations The major changes include recommendation of a booster dose of injectable polio vaccine (IPV) at 4–6 years for children who have received the initial IPV doses as per the ACVIP/IAP schedule, re-emphasis on the importance of IPV in the primary immunization schedule, preferred timing of second dose of varicella vaccine at 3–6 months after the first dose, and uniform dosing recommendation of 0.5 mL (15 µg HA) for inactivated influenza vaccines.
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8
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Paradis EM, Tikhonov O, Cao X, Kharit SM, Fokin A, Platt HL, Banniettis N. Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy adults. Hum Vaccin Immunother 2021; 17:4177-4182. [PMID: 34473594 DOI: 10.1080/21645515.2021.1957414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV). Adults typically experience more severe symptoms than children and have a higher risk of developing complications. Stage 1 of this Phase 3 open-label study enrolled healthy adults in Russia aged 18-75 years without a clinical history of varicella infection. Eligible participants (n = 50) were administered 2 doses of VARIVAX™ (Varicella Virus Vaccine Live [Oka/Merck]) 0.5 mL 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immuno-sorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and assessment of geometric mean titers of VZV antibody as measured by gpELISA 6 weeks after Dose 2. For VZV seropositive participants at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by geometric mean fold rise in antibody titer and percentage of participants with a ≥ 4-fold rise in antibody titer 6 weeks after Dose 2. A Vaccine Report Card was used to record solicited and unsolicited adverse events through 42 days post-vaccination. All participants who were seronegative (n = 26) at baseline demonstrated seroconversion 6 weeks after Dose 2. Among participants who were seropositive at baseline (n = 23), 60.9% had a ≥4-fold rise in antibody titer 6 weeks after Dose 2. Vaccination was generally well tolerated, with no new safety signals identified. Administration of 2 doses of VARIVAX in adults in Russia results in acceptable immune responses with safety data consistent with the licensed product (Clinicaltrials.gov identifier: NCT03843632).
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Affiliation(s)
| | | | - Xin Cao
- Merck & Co., Inc., Kenilworth, NJ, USA
| | - Susanna M Kharit
- Scientific Research Institute of Children's Infections of the Russian Federal Biomedical Agency, St. Petersburg, Russia
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Telenti A, Arvin A, Corey L, Corti D, Diamond MS, García-Sastre A, Garry RF, Holmes EC, Pang PS, Virgin HW. After the pandemic: perspectives on the future trajectory of COVID-19. Nature 2021; 596:495-504. [PMID: 34237771 DOI: 10.1038/s41586-021-03792-w] [Citation(s) in RCA: 239] [Impact Index Per Article: 59.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/01/2021] [Indexed: 02/07/2023]
Abstract
There is a realistic expectation that the global effort in vaccination will bring the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under control. Nonetheless, uncertainties remain about the type of long-term association that the virus will establish with the human population and, in particular, whether coronavirus disease 2019 (COVID-19) will become an endemic disease. Although the trajectory is difficult to predict, the conditions, concepts and variables that influence this transition can be anticipated. Persistence of SARS-CoV-2 as an endemic virus, perhaps with seasonal epidemic peaks, may be fuelled by pockets of susceptible individuals and waning immunity after infection or vaccination, changes in the virus through antigenic drift that diminish protection and re-entries from zoonotic reservoirs. Here we review relevant observations from previous epidemics and discuss the potential evolution of SARS-CoV-2 as it adapts during persistent transmission in the presence of a level of population immunity. Lack of effective surveillance or adequate response could enable the emergence of new epidemic or pandemic patterns from an endemic infection of SARS-CoV-2. There are key pieces of data that are urgently needed in order to make good decisions; we outline these and propose a way forward.
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Affiliation(s)
- Amalio Telenti
- Vir Biotechnology, San Francisco, CA, USA. .,Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.
| | - Ann Arvin
- Vir Biotechnology, San Francisco, CA, USA.
| | - Lawrence Corey
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
| | - Davide Corti
- Humabs Biomed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
| | - Michael S Diamond
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. .,Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. .,Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
| | - Adolfo García-Sastre
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Robert F Garry
- Department of Microbiology and Immunology, Tulane University, New Orleans, LA, USA.
| | - Edward C Holmes
- Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
| | | | - Herbert W Virgin
- Vir Biotechnology, San Francisco, CA, USA. .,Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. .,Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
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10
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Kasi SG, Shivananda S, Marathe S, Chatterjee K, Agarwalla S, Dhir SK, Verma S, Shah AK, Srirampur S, Kalyani S, Pemde HK, Balasubramanian S, Parekh BJ, Basavaraja GV, Gupta P. Indian Academy of Pediatrics (IAP) Advisory Committee on Vaccines and Immunization Practices (ACVIP): Recommended Immunization Schedule (2020-21) and Update on Immunization for Children Aged 0 Through 18 Years. Indian Pediatr 2021; 58:44-53. [PMID: 33257602 PMCID: PMC7840391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2023]
Abstract
JUSTIFICATION In view of new developments in vaccinology and the availability of new vaccines, there is a need to revise/review the existing immunization recommendations. PROCESS Advisory Committee on Vaccines and Immunization Practices (ACVIP) of Indian Academy of Pediatrics (IAP) had a physical meeting in March, 2020 followed by online meetings (September-October, 2020), to discuss the updates and new recommendations. Opinion of each member was sought on the various recommendations and updates, following which an evidence-based consensus was reached. OBJECTIVES To review and revise the IAP recommendations for 2020-21 and issue recommendations on existing and new vaccines. RECOMMENDATIONS The major changes include recommendation of a booster dose of injectable polio vaccine (IPV) at 4-6 years for children who have received the initial IPV doses as per the ACVIP/IAP schedule, re-emphasis on the importance of IPV in the primary immunization schedule, preferred timing of second dose of varicella vaccine at 3-6 months after the first dose, and uniform dosing recommendation of 0.5 mL (15 µg HA) for inactivated influenza vaccines.
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Affiliation(s)
- Srinivas G Kasi
- Kasi Clinic, Jayanagar, Bengaluru, Karnataka, India. Correspondence to: Srinivas G Kasi, Convener, ACVIP, Kasi Clinic, 2nd Cross, 3rd Block, Jayanagar, Bengaluru 560011, Karnataka, India.
| | - S Shivananda
- Fortis Hospital, Banneraghatta Road, Bengaluru, Karnataka, India
| | | | - Kripasindhu Chatterjee
- Department of Pediatrics, Gouri Devi Institute of Medical Science and Hospital, Durgapur, Paschim Bardhaman, West Bengal, India
| | - Sunil Agarwalla
- Department of Pediatrics, MKCG MCH, Berhampur, Odisha, India
| | - Shashi Kant Dhir
- Department of Pediatrics, Guru Gobind Singh Medical College, Faridkot, Punjab, India
| | - Sanjay Verma
- Division of Infectious Diseases, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Abhay K Shah
- Dr Abhay K Shah Children Hospital, Ahmedabad, Gujarat, India
| | - Sanjay Srirampur
- Department of Pediatrics, Aditya Super speciality Hospital, Hyderabad, Telangana, India
| | - Srinivas Kalyani
- Department of Pediatrics, Niloufer Hospital, Osmania medical College, Hyderabad, India
| | - Harish Kumar Pemde
- Department of Pediatrics, Lady Hardinge Medical College, New Delhi, India
| | - S Balasubramanian
- Department of Pediatrics, Kanchi Kamakoti Childs Trust Hospital, Chennai, Tamil Nadu, India
| | | | - G V Basavaraja
- Department of Pediatrics, IGICH, Bengaluru, Karnataka, India
| | - Piyush Gupta
- Department of Pediatrics, University College of Medical Sciences, New Delhi; India
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11
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Elahi S. Neonatal and Children’s Immune System and COVID-19: Biased Immune Tolerance versus Resistance Strategy. THE JOURNAL OF IMMUNOLOGY 2020; 205:1990-1997. [DOI: 10.4049/jimmunol.2000710] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Abstract
The recent outbreak of COVID-19 has emerged as a major global health concern. Although susceptible to infection, recent evidence indicates mostly asymptomatic or mild presentation of the disease in infants, children, and adolescents. Similar observations were made for acute respiratory infections caused by other coronaviruses (severe acute respiratory syndrome and Middle East respiratory syndrome). These observations suggest that the immune system behaves differently in children than adults. Recent developments in the field demonstrated fundamental differences in the neonatal immune system as compared with adults, whereby infants respond to microorganisms through biased immune tolerance rather than resistance strategies. Similarly, more frequent/recent vaccinations in children and younger populations may result in trained immunity. Therefore, the physiological abundance of certain immunosuppressive cells, a tightly regulated immune system, and/or exposure to attenuated vaccines may enhance trained immunity to limit excessive immune reaction to COVID-19 in the young.
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Affiliation(s)
- Shokrollah Elahi
- School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G2E1, Canada
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta T6G1Z2, Canada
- Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G2E1, Canada; and
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta T6G2E1, Canada
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Abstract
Purpose of review Varicella zoster virus (VZV) is a highly contagious, neurotropic alpha herpes virus that causes varicella (chickenpox). VZV establishes lifelong latency in the sensory ganglia from which it can reactivate to induce herpes zoster (HZ), a painful disease that primarily affects older individuals and those who are immune-suppressed. Given that VZV infection is highly specific to humans, developing a reliable in vivo model that recapitulates the hallmarks of VZV infection has been challenging. Simian Varicella Virus (SVV) infection in nonhuman primates reproduces the cardinal features of VZV infections in humans and allows the study of varicella virus pathogenesis in the natural host. In this review, we summarize our current knowledge about genomic and virion structure of varicelloviruses as well as viral pathogenesis and antiviral immune responses during acute infection, latency and reactivation. We also examine the immune evasion mechanisms developed by varicelloviruses to escape the host immune responses and the current vaccines available for protecting individuals against chickenpox and herpes zoster. Recent findings Data from recent studies suggest that infected T cells are important for viral dissemination to the cutaneous sites of infection as well as site of latency and that a viral latency-associated transcript might play a role in the transition from lytic infection to latency and then reactivation. Summary Recent studies have provided exciting insights into mechanisms of varicelloviruses pathogenesis such as the critical role of T cells in VZV/SVV dissemination from the respiratory mucosa to the skin and the sensory ganglia; the ability of VZV/SVV to interfere with host defense; and the identification of VLT transcripts in latently infected ganglia. However, our understanding of these phenomena remains poorly understood. Therefore, it is critical that we continue to investigate host-pathogen interactions during varicelloviruses infection. These studies will lead to a deeper understanding of VZV biology as well as novel aspects of cell biology.
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Mitra M, Chowdhury J, Basu S, Halder PP, Mukherjee M, Karadkhele A, Puppalwar G, Jain R. Evaluation of immunogenicity, safety and breakthrough following administration of live attenuated varicella vaccine in two doses three months apart regimen in Indian children. Ther Adv Vaccines Immunother 2020; 8:2515135520937216. [PMID: 32851202 PMCID: PMC7425319 DOI: 10.1177/2515135520937216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 05/28/2020] [Indexed: 11/15/2022] Open
Abstract
Background: In India, where varicella outbreaks are reported at a younger age, a two-dose vaccine schedule administered at an early age could be highly efficacious in preventing varicella infection. The aim of this study was to evaluate the immunogenicity and safety of live attenuated varicella vaccine (VR 795 Oka strain) in a two-dose, 3 months apart regimen. Methodology: Healthy children (⩾ 12 months and ⩽12 years; mean age: 4.4 years) of either sex were included. Geometric mean titers (GMT) were measured at baseline and 28 days post first- and second-dose, and seroprotection rates were measured 28 days post first and second dose. The incidence of breakthrough (BT) infections post vaccination was determined from 42 days post first and second dose of vaccine up to 12 months. Adverse events (AEs) were monitored and recorded throughout the study period. Results: Of 305 subjects enrolled, 217 were seronegative. The seroconversion rate (a change from a seronegative to a seropositive condition) was 93.3% post first-dose and 100% post two-doses. High levels (9 times) of GMT were reported since post first-dose to post second-dose in children aged 12–18 months, 18–60 months (99.43%); and in and above 60 months (99.02%). The extent of rise of anti-VZV IgG antibody titer post 28 days of first-dose at two-fold, three-fold and four-fold rise was 93.39%, 90.56% and 80.66%, respectively and 100% 4-fold rise post second-dose. A single case, a day after the first-dose of vaccination of mild BT infection, was observed after close contact with a severe case. AEs were mild and none of the serious AEs were related to the study drug. Conclusion: The two-dose schedule of varicella vaccine was safe and immunogenic when given 3 months apart. However, further comparative studies and follow up for both dosing schedules are needed to validate the advantage of early dosing.
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Affiliation(s)
| | | | | | | | | | - Archana Karadkhele
- Medical Affairs Division, Wockhardt Ltd., 1st Floor, West Wing, Wockhardt Global Headquarters, Bandra Kurla Complex, Bandra (East), Mumbai-51, India
| | | | - Rishi Jain
- Medical Affairs Division, Wockhardt Ltd., Mumbai, India
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Persistence of Varicella-Zoster Virus-Specific Plasma Cells in Adult Human Bone Marrow following Childhood Vaccination. J Virol 2020; 94:JVI.02127-19. [PMID: 32321817 DOI: 10.1128/jvi.02127-19] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 03/26/2020] [Indexed: 01/30/2023] Open
Abstract
Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults (n = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow.IMPORTANCE Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity.
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15
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Iritani R, Visher E, Boots M. The evolution of stage-specific virulence: Differential selection of parasites in juveniles. Evol Lett 2019; 3:162-172. [PMID: 31289690 PMCID: PMC6591554 DOI: 10.1002/evl3.105] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 02/12/2019] [Indexed: 11/05/2022] Open
Abstract
The impact of infectious disease is often very different in juveniles and adults, but theory has focused on the drivers of stage-dependent defense in hosts rather than the potential for stage-dependent virulence evolution in parasites. Stage structure has the potential to be important to the evolution of pathogens because it exposes parasites to heterogeneous environments in terms of both host characteristics and transmission pathways. We develop a stage-structured (juvenile-adult) epidemiological model and examine the evolutionary outcomes of stage-specific virulence under the classic assumption of a transmission-virulence trade-off. We show that selection on virulence against adults remains consistent with the classic theory. However, the evolution of juvenile virulence is sensitive to both demography and transmission pathway with higher virulence against juveniles being favored either when the transmission pathway is assortative (juveniles preferentially interact together) and the juvenile stage is long, or in contrast when the transmission pathway is disassortative and the juvenile stage is short. These results highlight the potentially profound effects of host stage structure on determining parasite virulence in nature. This new perspective may have broad implications for both understanding and managing disease severity.
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Affiliation(s)
- Ryosuke Iritani
- Biosciences, College of Life and Environmental ScienceUniversity of ExeterExeterUnited Kingdom
- Department of Integrative BiologyUniversity of California3040 Valley Life Sciences Building #3140BerkeleyCA94720
| | - Elisa Visher
- Department of Integrative BiologyUniversity of California3040 Valley Life Sciences Building #3140BerkeleyCA94720
| | - Mike Boots
- Biosciences, College of Life and Environmental ScienceUniversity of ExeterExeterUnited Kingdom
- Department of Integrative BiologyUniversity of California3040 Valley Life Sciences Building #3140BerkeleyCA94720
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16
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Sorel O, Messaoudi I. Varicella Virus-Host Interactions During Latency and Reactivation: Lessons From Simian Varicella Virus. Front Microbiol 2018; 9:3170. [PMID: 30619226 PMCID: PMC6308120 DOI: 10.3389/fmicb.2018.03170] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 12/07/2018] [Indexed: 01/11/2023] Open
Abstract
Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus and the causative agent of varicella (chickenpox) in humans. Following primary infection, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster, more commonly known as shingles, which causes significant morbidity, and on rare occasions mortality, in the elderly. Because VZV infection is highly restricted to humans, the development of a reliable animal model has been challenging, and our understanding of VZV pathogenesis remains incomplete. As an alternative, infection of rhesus macaques with the homologous simian varicella virus (SVV) recapitulates the hallmarks of VZV infection and thus constitutes a robust animal model to provide critical insights into VZV pathogenesis and the host antiviral response. In this model, SVV infection results in the development of varicella during primary infection, generation of an adaptive immune response, establishment of latency in the sensory ganglia, and viral reactivation upon immune suppression. In this review, we discuss our current knowledge about host and viral factors involved in the establishment of SVV latency and reactivation as well as the important role played by T cells in SVV pathogenesis and antiviral immunity.
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Affiliation(s)
- Océane Sorel
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, United States
| | - Ilhem Messaoudi
- Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, United States
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17
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Jamani K, MacDonald J, Lavoie M, Williamson TS, Brown CB, Chaudhry A, Jimenez-Zepeda VH, Duggan P, Tay J, Stewart D, Daly A, Storek J. Zoster prophylaxis after allogeneic hematopoietic cell transplantation using acyclovir/valacyclovir followed by vaccination. Blood Adv 2016; 1:152-159. [PMID: 29296807 PMCID: PMC5737163 DOI: 10.1182/bloodadvances.2016000836] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 10/16/2016] [Indexed: 11/20/2022] Open
Abstract
Varicella zoster virus (VZV) disease (usually cutaneous zoster) occurs frequently after hematopoietic cell transplantation (HCT), and postherpetic neuralgia (PHN) results in poor quality of life. The optimal prophylaxis of VZV disease/PHN has not been established. At our center, before 2008, VZV prophylaxis consisted of ∼1 year of post-HCT acyclovir/valacyclovir ("old strategy"), whereas post-2008 prophylaxis consisted of 2 years of acyclovir/valacyclovir followed by immunization using varicella vaccine ("new strategy"). We performed a retrospective study comparing the cumulative incidence of VZV disease and PHN among patients who completed the old strategy (n = 153) vs the new strategy (n = 125). Patients who completed the old strategy had a significantly higher cumulative incidence of VZV disease (33% vs 17% at 5 years, P ≤ .01) and PHN (8% vs 0% at 5 years, P = .02). In conclusion, VZV prophylaxis with 2 years of acyclovir/valacyclovir followed by vaccination appears to result in a low incidence of VZV disease and may eliminate PHN.
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Affiliation(s)
- Kareem Jamani
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
| | - Judy MacDonald
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Population, Public and Aboriginal Health, Alberta Health Services, Calgary, AB, Canada; and
| | - Martin Lavoie
- Alberta Health, Government of Alberta, Edmonton, AB, Canada
| | - Tyler S Williamson
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Christopher B Brown
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
| | - Ahsan Chaudhry
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
| | - Victor H Jimenez-Zepeda
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
| | - Peter Duggan
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
| | - Jason Tay
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
| | - Douglas Stewart
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
| | - Andrew Daly
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
| | - Jan Storek
- Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada
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18
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Ullmann AJ, Schmidt-Hieber M, Bertz H, Heinz WJ, Kiehl M, Krüger W, Mousset S, Neuburger S, Neumann S, Penack O, Silling G, Vehreschild JJ, Einsele H, Maschmeyer G. Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol 2016; 95:1435-55. [PMID: 27339055 PMCID: PMC4972852 DOI: 10.1007/s00277-016-2711-1] [Citation(s) in RCA: 131] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/28/2016] [Indexed: 12/13/2022]
Abstract
Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria.
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Affiliation(s)
- Andrew J Ullmann
- Department of Internal Medicine II, Division of Hematology and Oncology, Division of Infectious Diseases, Universitätsklinikum, Julius Maximilian's University, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
| | - Martin Schmidt-Hieber
- Clinic for Hematology, Oncology und Tumor Immunology, Helios Clinic Berlin-Buch, Berlin, Germany
| | - Hartmut Bertz
- Department of Hematology/Oncology, University of Freiburg Medical Center, 79106, Freiburg, Germany
| | - Werner J Heinz
- Department of Internal Medicine II, Division of Hematology and Oncology, Division of Infectious Diseases, Universitätsklinikum, Julius Maximilian's University, Oberdürrbacher Str. 6, 97080, Würzburg, Germany
| | - Michael Kiehl
- Medical Clinic I, Klinikum Frankfurt (Oder), Frankfurt (Oder), Germany
| | - William Krüger
- Haematology and Oncology, Stem Cell Transplantation, Palliative Care, University Hospital Greifswald, Greifswald, Germany
| | - Sabine Mousset
- Medizinische Klinik III, Palliativmedizin und interdisziplinäre Onkologie, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany
| | - Stefan Neuburger
- Sindelfingen-Böblingen Clinical Centre, Medical Department I, Division of Hematology and Oncology, Klinikverbund Südwest, Sindelfingen, Germany
| | | | - Olaf Penack
- Hematology, Oncology and Tumorimmunology, Charité University Medicine Berlin, Campus Virchow Klinikum, Berlin, Germany
| | - Gerda Silling
- Department of Internal Medicine IV, University Hospital RWTH Aachen, Aachen, Germany
| | - Jörg Janne Vehreschild
- Department I of Internal Medicine, German Centre for Infection Research, Partner-site: Bonn-Cologne, University Hospital of Cologne, Cologne, Germany
| | - Hermann Einsele
- Department of Internal Medicine II, Division of Hematology and Oncology, Division of Infectious Diseases, Universitätsklinikum, Julius Maximilian's University, Oberdürrbacher Str. 6, 97080, Würzburg, Germany
| | - Georg Maschmeyer
- Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany
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19
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De Paschale M, Clerici P. Microbiology laboratory and the management of mother-child varicella-zoster virus infection. World J Virol 2016; 5:97-124. [PMID: 27563537 PMCID: PMC4981827 DOI: 10.5501/wjv.v5.i3.97] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 07/08/2016] [Accepted: 07/22/2016] [Indexed: 02/05/2023] Open
Abstract
Varicella-zoster virus, which is responsible for varicella (chickenpox) and herpes zoster (shingles), is ubiquitous and causes an acute infection among children, especially those aged less than six years. As 90% of adults have had varicella in childhood, it is unusual to encounter an infected pregnant woman but, if the disease does appear, it can lead to complications for both the mother and fetus or newborn. The major maternal complications include pneumonia, which can lead to death if not treated. If the virus passes to the fetus, congenital varicella syndrome, neonatal varicella (particularly serious if maternal rash appears in the days immediately before or after childbirth) or herpes zoster in the early years of life may occur depending on the time of infection. A Microbiology laboratory can help in the diagnosis and management of mother-child infection at four main times: (1) when a pregnant woman has been exposed to varicella or herpes zoster, a prompt search for specific antibodies can determine whether she is susceptible to, or protected against infection; (2) when a pregnant woman develops clinical symptoms consistent with varicella, the diagnosis is usually clinical, but a laboratory can be crucial if the symptoms are doubtful or otherwise unclear (atypical patterns in immunocompromised subjects, patients with post-vaccination varicella, or subjects who have received immunoglobulins), or if there is a need for a differential diagnosis between varicella and other types of dermatoses with vesicle formation; (3) when a prenatal diagnosis of uterine infection is required in order to detect cases of congenital varicella syndrome after the onset of varicella in the mother; and (4) when the baby is born and it is necessary to confirm a diagnosis of varicella (and its complications), make a differential diagnosis between varicella and other diseases with similar symptoms, or confirm a causal relationship between maternal varicella and malformations in a newborn.
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20
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MAPLE PAC, HAEDICKE J, QUINLIVAN M, STEINBERG SP, GERSHON AA, BROWN KE, BREUER J. The differences in short- and long-term varicella-zoster virus (VZV) immunoglobulin G levels following varicella vaccination of healthcare workers measured by VZV fluorescent-antibody-to-membrane-antigen assay (FAMA), VZV time-resolved fluorescence immunoassay and a VZV purified glycoprotein enzyme immunoassay. Epidemiol Infect 2016; 144:2345-53. [PMID: 27018820 PMCID: PMC5726866 DOI: 10.1017/s0950268816000595] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 02/04/2016] [Accepted: 03/02/2016] [Indexed: 01/31/2023] Open
Abstract
Healthcare workers (HCWs) reporting no history of varicella frequently receive varicella vaccination (vOka) if they test varicella-zoster virus (VZV) immunoglobulin G (IgG) negative. In this study, the utilities of VZV-IgG time-resolved fluorescence immunoassay (VZV-TRFIA) and a commercial VZV-IgG purified glycoprotein enzyme immunoassay (gpEIA) currently used in England for confirming VZV immunity have been compared to the fluorescent-antibody-to-membrane-antigen assay (FAMA). A total of 110 HCWs received two doses of vOka vaccine spaced 6 weeks apart and sera collected pre-vaccination (n = 100), at 6 weeks post-completion of vaccination (n = 86) and at 12-18 months follow-up (n = 73) were analysed. Pre-vaccination, by FAMA, 61·0% sera were VZV IgG negative, and compared to FAMA the sensitivities of VZV-TRFIA and gpEIA were 74·4% [95% confidence interval (CI) 57·9-87·0] and 46·2% (95% CI 30·1-62·8), respectively. Post-completion of vaccination the seroconversion rate by FAMA was 93·7% compared to rates of 95·8% and 70·8% determined by VZV-TRFIA and gpEIA, respectively. At 12-18 months follow-up seropositivity rates by FAMA, VZV-TRFIA and gpEIA were 78·1%, 74·0% and 47·9%, respectively. Compared to FAMA the sensitivities of VZV-TRFIA and gpEIA for measuring VZV IgG following vaccination were 96·4% (95% CI 91·7-98·8) and 74·6% (95% CI 66·5-81·6), respectively. Using both FAMA and VZV-TRFIA to identify healthy adult VZV susceptibles and measure seroconversion showed that vOka vaccination of HCWs is highly immunogenic.
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Affiliation(s)
- P. A. C. MAPLE
- Virus Reference Department, Public Health England, Reference Microbiology Services, Colindale, London, UK
- East Yorkshire Microbiology, York Science Park, Heslington, York, UK
| | - J. HAEDICKE
- Department of Infection, The Cruciform Building, University College London, London, UK
| | - M. QUINLIVAN
- Department of Infection, The Cruciform Building, University College London, London, UK
| | - S. P. STEINBERG
- Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, USA
| | - A. A. GERSHON
- Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, USA
| | - K. E. BROWN
- Virus Reference Department, Public Health England, Reference Microbiology Services, Colindale, London, UK
| | - J. BREUER
- Department of Infection, The Cruciform Building, University College London, London, UK
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21
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Abortive intrabronchial infection of rhesus macaques with varicella-zoster virus provides partial protection against simian varicella virus challenge. J Virol 2014; 89:1781-93. [PMID: 25410871 DOI: 10.1128/jvi.03124-14] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
UNLABELLED Varicella-zoster virus (VZV) is a human neurotropic alphaherpesvirus and the etiological agent of varicella (chickenpox) and herpes zoster (HZ, shingles). Previously, inoculation of monkeys via the subcutaneous, intratracheal, intravenous, or oral-nasal-conjunctival routes did not recapitulate all the hallmarks of VZV infection, including varicella, immunity, latency, and reactivation. Intrabronchial inoculation of rhesus macaques (RMs) with simian varicella virus (SVV), a homolog of VZV, recapitulates virologic and immunologic hallmarks of VZV infection in humans. Given that VZV is acquired primarily via the respiratory route, we investigated whether intrabronchial inoculation of RMs with VZV would result in a robust model. Despite the lack of varicella and viral replication in either the lungs or whole blood, all four RMs generated an immune response characterized by the generation of VZV-specific antibodies and T cells. Two of 4 VZV-inoculated RMs were challenged with SVV to determine cross-protection. VZV-immune RMs displayed no varicella rash and had lower SVV viral loads and earlier and stronger humoral and cellular immune responses than controls. In contrast to the results for SVV DNA, no VZV DNA was detected in sensory ganglia at necropsy. In summary, following an abortive VZV infection, RMs developed an adaptive immune response that conferred partial protection against SVV challenge. These data suggest that a replication-incompetent VZV vaccine that does not establish latency may provide sufficient protection against VZV disease and that VZV vaccination of RMs followed by SVV challenge provides a model to evaluate new vaccines and therapeutics against VZV. IMPORTANCE Although VZV vaccine strain Oka is attenuated, it can cause mild varicella, establish latency, and in rare cases, reactivate to cause herpes zoster (HZ). Moreover, studies suggest that the HZ vaccine (Zostavax) only confers short-lived immunity. The development of more efficacious vaccines would be facilitated by a robust animal model of VZV infection. The data presented in this report show that intrabronchial inoculation of rhesus macaques (RMs) with VZV resulted in an abortive VZV infection. Nevertheless, all animals generated a humoral and cellular immune response that conferred partial cross-protection against simian varicella virus (SVV) challenge. Additionally, VZV DNA was not detected in the sensory ganglia, suggesting that viremia might be required for the establishment of latency. Therefore, VZV vaccination of RMs followed by SVV challenge is a model that will support the development of vaccines that boost protective T cell responses against VZV.
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Papaloukas O, Giannouli G, Papaevangelou V. Successes and challenges in varicella vaccine. THERAPEUTIC ADVANCES IN VACCINES 2014; 2:39-55. [PMID: 24757524 DOI: 10.1177/2051013613515621] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Varicella is a highly contagious disease caused by primary infection with varicella zoster virus (VZV). VZV infection, as well as varicella vaccination, induces VZV-specific antibody and T-cell-mediated immunity, essential for recovery. The immune responses developed contribute to protection following re-exposure to VZV. When cell-mediated immunity declines, as occurs with aging or immunosuppression, reactivation of VZV leads to herpes zoster (HZ). It has been almost 20 years since universal varicella vaccination has been implemented in many areas around the globe and this has resulted in a significant reduction of varicella-associated disease burden. Successes are reviewed here, whilst emphasis is put on the challenges ahead. Most countries that have not implemented routine childhood varicella vaccination have chosen to vaccinate high-risk groups alone. The main reasons for not introducing universal vaccination are discussed, including fear of age shift of peak incidence age and of HZ incidence increase. Possible reasons for not observing the predicted increase in HZ incidence are explored. The advantages and disadvantages of universal vs targeted vaccination as well as different vaccination schedules are discussed.
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Affiliation(s)
- Orestis Papaloukas
- Second Department of Pediatrics, University of Athens Medical School, P&A Kyriakou Childrens' Hospital, Greece
| | - Georgia Giannouli
- Second Department of Pediatrics, University of Athens Medical School, P&A Kyriakou Childrens' Hospital, Greece
| | - Vassiliki Papaevangelou
- Third Department of Pediatrics, University of Athens Medical School, General University Hospital 'ATTIKON', Rimini 1, Chaidari 124 62, Greece
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23
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Macartney K, Heywood A, McIntyre P, Cochrane Acute Respiratory Infections Group. Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults. Cochrane Database Syst Rev 2014; 2014:CD001833. [PMID: 24954057 PMCID: PMC7061782 DOI: 10.1002/14651858.cd001833.pub3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND The prevention of varicella (chickenpox) using live attenuated varicella vaccines has been demonstrated both in randomised controlled trials (RCTs) and in population-based immunisation programmes in countries such as the United States and Australia. Many countries do not routinely immunise children against varicella and exposures continue to occur. Although the disease is often mild, complications such as secondary bacterial infection, pneumonitis and encephalitis occur in about 1% of cases, usually leading to hospitalisation. The use of varicella vaccine in persons who have recently been exposed to the varicella zoster virus has been studied as a form of post-exposure prophylaxis (PEP). OBJECTIVES To assess the efficacy and safety of vaccines for use as PEP for the prevention of varicella in children and adults. SEARCH METHODS We searched CENTRAL (2014, Issue 1), MEDLINE (1966 to March week 1, 2014), EMBASE (January 1990 to March 2014) and LILACS (1982 to March 2014). We searched for unpublished trials registered on the clinicaltrials.gov and WHO ICTRP websites. SELECTION CRITERIA RCTs and quasi-RCTs of varicella vaccine for PEP compared with placebo or no intervention. The outcome measures were efficacy in prevention of clinical cases and/or laboratory-confirmed clinical cases and adverse events following vaccination. DATA COLLECTION AND ANALYSIS Two review authors independently extracted and analysed data using Review Manager software. MAIN RESULTS We identified three trials involving 110 healthy children who were siblings of household contacts. The included trials varied in study quality, vaccine used, length of follow-up and outcomes measured and, as such, were not suitable for meta-analysis. We identified high or unclear risk of bias in two of the three included studies. Overall, 13 out of 56 vaccine recipients (23%) developed varicella compared with 42 out of 54 placebo (or no vaccine) recipients (78%). Of the vaccine recipients who developed varicella, the majority only had mild disease (with fewer than 50 skin lesions). In the three trials, most participants received PEP within three days following exposure; too few participants were vaccinated four to five days post-exposure to ascertain the efficacy of vaccine given more than three days after exposure. No included trial reported on adverse events following immunisation. AUTHORS' CONCLUSIONS These small trials suggest varicella vaccine administered within three days to children following household contact with a varicella case reduces infection rates and severity of cases. We identified no RCTs for adolescents or adults. Safety was not adequately addressed.
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Affiliation(s)
- Kristine Macartney
- Children's Hospital at Westmead and University of SydneyNational Centre for Immunisation Research and Surveillance of Vaccine Preventable DiseasesLocked Bag 4001WestmeadSydneyNSWAustralia2145
| | - Anita Heywood
- University of New South WalesSchool of Public Health and Community MedicineLevel 2, Samuels BuildingGate 11, Botany StreetKensingtonNSWAustralia2052
| | - Peter McIntyre
- Children's Hospital at Westmead and University of SydneyNational Centre for Immunisation Research and Surveillance of Vaccine Preventable DiseasesLocked Bag 4001WestmeadSydneyNSWAustralia2145
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Age and immune status of rhesus macaques impact simian varicella virus gene expression in sensory ganglia. J Virol 2013; 87:8294-306. [PMID: 23698305 DOI: 10.1128/jvi.01112-13] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Simian varicella virus (SVV) infection of rhesus macaques (RMs) recapitulates the hallmarks of varicella-zoster virus (VZV) infection of humans, including the establishment of latency within the sensory ganglia. Various factors, including age and immune fitness, influence the outcome of primary VZV infection, as well as reactivation resulting in herpes zoster (HZ). To increase our understanding of the role of lymphocyte subsets in the establishment of viral latency, we analyzed the latent SVV transcriptome in juvenile RMs depleted of CD4 T, CD8 T, or CD20 B lymphocytes during acute infection. We have previously shown that SVV latency in sensory ganglia of nondepleted juvenile RMs is associated with a limited transcriptional profile. In contrast, CD4 depletion during primary infection resulted in the failure to establish a characteristic latent viral transcription profile in sensory ganglia, where we detected 68 out of 69 SVV-encoded open reading frames (ORFs). CD-depleted RMs displayed a latent transcriptional profile that included additional viral transcripts within the core region of the genome not detected in control RMs. The latent transcriptome of CD20-depleted RMs was comparable to the latent transcription in the sensory ganglia of control RMs. Lastly, we investigated the impact of age on the establishment of SVV latency. SVV gene expression was more active in ganglia from two aged RMs than in ganglia from juvenile RMs, with 25 of 69 SVV transcripts detected. Therefore, immune fitness at the time of infection modulates the establishment and/or maintenance of SVV latency.
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Varicella pneumonia complicating pregnancy: a report of seven cases. Infect Dis Obstet Gynecol 2012; 4:338-46. [PMID: 18476122 PMCID: PMC2364517 DOI: 10.1155/s1064744996000683] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/1996] [Accepted: 01/14/1997] [Indexed: 01/30/2023] Open
Abstract
Background: Pneumonia is the most common complication of varicella-zoster infection in adults and
has potentially devastating effects when complicating pregnancy. Due to the significant morbidity
and mortality associated with this complication during pregnancy and the small number of reported
cases in the literature, we present this report to help educate physicians who care for pregnant
women. Cases: Seven patients are presented in this report. These patients presented at various stages in
pregnancy, from 17 to 31 weeks of gestation. Three of the patients had unremarkable hospital
courses. Three of the patients had hospital stays over 21 days in duration. One patient died from
complications of varicella pneumonia after 31 days of hospitalization. The obstetric outcomes of the
7 patients described include 1 non-viable delivery at 20 weeks gestation, 3 term deliveries, 2 preterm
deliveries, and 1 patient who has not yet delivered. All of the patients presented were treated with
intravenous acyclovir therapy. Of the patients described, 3 required intubation and ventilatory
support. Other complications encountered include disseminated intravascular coagulation (DIC),
adult respiratory distress syndrome (ARDS), metabolic encephalopathy, pneumothorax, superimposed
bacterial pneumonia, and sepsis. Conclusion: The course and treatment of varicella pneumonia complicating pregnancy are discussed.
Current recommendations regarding the use of varicella-zoster immune globulin (VZIG)
are also reviewed.
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Knuf M, Zepp F, Helm K, Maurer H, Prieler A, Kieninger-Baum D, Douha M, Willems P. Antibody persistence for 3 years following two doses of tetravalent measles-mumps-rubella-varicella vaccine in healthy children. Eur J Pediatr 2012; 171:463-70. [PMID: 21935584 DOI: 10.1007/s00431-011-1569-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Accepted: 09/05/2011] [Indexed: 11/28/2022]
Abstract
UNLABELLED Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12-18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42-56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42-56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15-20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. CONCLUSION Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211).
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Affiliation(s)
- Markus Knuf
- Children's Department of Pediatrics, University Medicine Hospital, Johannes Gutenberg-University, Langenbeckstrasse 1, 55101 Mainz, Germany.
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Haberthur K, Engelmann F, Park B, Barron A, Legasse A, Dewane J, Fischer M, Kerns A, Brown M, Messaoudi I. CD4 T cell immunity is critical for the control of simian varicella virus infection in a nonhuman primate model of VZV infection. PLoS Pathog 2011; 7:e1002367. [PMID: 22102814 PMCID: PMC3213099 DOI: 10.1371/journal.ppat.1002367] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2011] [Accepted: 09/22/2011] [Indexed: 11/19/2022] Open
Abstract
Primary infection with varicella zoster virus (VZV) results in varicella (more commonly known as chickenpox) after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles), a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax) and herpes zoster (Zostavax) are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, albeit rarely, in children and a 2-dose regimen is now recommended. Similarly, although Zostavax results in a 50% reduction in HZ cases, a significant number of recipients remain at risk. To design more efficacious vaccines, we need a better understanding of the immune response to VZV. Clinical observations suggest that T cell immunity plays a more critical role in the protection against VZV primary infection and reactivation. However, no studies to date have directly tested this hypothesis due to the scarcity of animal models that recapitulate the immune response to VZV. We have recently shown that SVV infection of rhesus macaques models the hallmarks of primary VZV infection in children. In this study, we used this model to experimentally determine the role of CD4, CD8 and B cell responses in the resolution of primary SVV infection in unvaccinated animals. Data presented in this manuscript show that while CD20 depletion leads to a significant delay and decrease in the antibody response to SVV, loss of B cells does not alter the severity of varicella or the kinetics/magnitude of the T cell response. Loss of CD8 T cells resulted in slightly higher viral loads and prolonged viremia. In contrast, CD4 depletion led to higher viral loads, prolonged viremia and disseminated varicella. CD4 depleted animals also had delayed and reduced antibody and CD8 T cell responses. These results are similar to clinical observations that children with agammaglobulinemia have uncomplicated varicella whereas children with T cell deficiencies are at increased risk of progressive varicella with significant complications. Moreover, our studies indicate that CD4 T cell responses to SVV play a more critical role than antibody or CD8 T cell responses in the control of primary SVV infection and suggest that one potential mechanism for enhancing the efficacy of VZV vaccines is by eliciting robust CD4 T cell responses. Varicella zoster virus (VZV) causes chickenpox and establishes a life-long latent infection in humans. VZV can reactivate years later to cause shingles, a debilitating and painful disease. Vaccines against both chickenpox and shingles are available but not 100% efficacious. Two doses of the chickenpox vaccine are required to provide adequate protection and the shingles vaccine reduces the incidence of this disease by 51%. To improve these vaccines, we must identify the components of the immune system that are important for the control of VZV replication. However, the contribution of T versus B cell responses is unknown. Infection of rhesus macaques with simian varicella virus is a robust model of VZV infection. Here, we used this unique animal model to show for the first time that the absence of B cells does not alter disease severity and that the loss of CD8 T cells only results in a mild increase in disease severity. In sharp contrast, the lack of CD4 T cells leads to disseminated varicella. These data highlight the importance of CD4 T cells and suggest that novel vaccines that focus on engendering a more robust CD4 T cell response against VZV might provide better protection from chickenpox and shingles.
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Affiliation(s)
- Kristen Haberthur
- Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, United States of America
- Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America
| | - Flora Engelmann
- Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America
| | - Byng Park
- Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, Oregon, United States of America
| | - Alex Barron
- Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America
| | - Alfred Legasse
- Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America
| | - Jesse Dewane
- Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America
| | - Miranda Fischer
- Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America
| | - Amelia Kerns
- Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America
| | - Monica Brown
- Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America
| | - Ilhem Messaoudi
- Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, United States of America
- Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America
- Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America
- * E-mail:
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Abstract
Primary varicella-zoster virus (VZV) infection (varicella) induces VZV-specific antibody and VZV-specific T cell-mediated immunity. T cell-mediated immunity, which is detected within 1-2 weeks after appearance of rash, and consists of both CD4 and CD8 effector and memory T cells, is essential for recovery from varicella. Administration of a varicella vaccine also generates VZV-specific humoral and cellular immune responses. The memory cell responses that develop during varicella or after vaccination contribute to protection following re-exposure to VZV. These responses are subsequently boosted either by endogenous re-exposure (silent reactivation of latent virus) or exogenous re-exposure (environmental). VZV-specific T cell-mediated immunity is also necessary to maintain latent VZV in a subclinical state in sensory ganglia. When these responses decline, as occurs with aging or iatrogenic immune suppression, reactivation of VZV leads to herpes zoster. Similarly, the magnitude of these responses early after the onset of herpes zoster correlates with the extent of zoster-associated pain. These essential immune responses are boosted by the VZV vaccine developed to prevent herpes zoster.
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Parment PA, Svahn A, Rudén U, Bråkenhielm G, Storsaeter J, Akesson L, Linde A. Immunogenicity and Reactogenicity of a Single Dose of Live Attenuated Varicella Vaccine and a Booster Dose of Measles–Mumps–Rubella Vaccine Given Concomitantly at 12 years of Age. ACTA ACUST UNITED AC 2010; 35:736-42. [PMID: 14606613 DOI: 10.1080/00365540310015719] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Universal varicella-zoster virus (VZV) childhood vaccination is still debated, but adult chickenpox may be severe. It could be prevented by vaccination of seronegative adolescents. This study aimed to determine the feasibility of coadministration of a VZV vaccine and the measles-mumps-rubella (MMR) booster at 12 y of age. Guardians of 1231 12-y-old pupils where asked about the history of chickenpox in their children. 190 had no chickenpox history and 12 of 62 of them lacked VZV antibodies. Additional history-negative children were also recruited. 199 history-positive children received only MMR and 98 history-negative children received an MMR vaccine and a VZV vaccine. Serum samples were drawn before vaccination and after 8 weeks. Viral antibodies were measured by immunofluorescence (VZV) and enzyme-linked immunosorbent assays (VZV, MMR). All 184 history-positive children tested had VZV antibodies. 17/89 VZV-vaccinated and tested children (19%) lacked VZV antibodies before vaccination. 12 (71%) seroconverted after 1 dose. Cell-mediated immunity (CMI) against varicella was tested in 3/5 children who did not seroconvert after 1 dose of VZV vaccine. They seroconverted after a second dose and had measurable CMI. VZV vaccination did not affect the MMR response and there were no severe side-effects. A history of varicella infection, as reported by the guardian, is reliable, but a negative history was incorrect in 81% of the cases. This population of 12-y-old children may require 2 doses of VZV vaccine, at least when given simultaneously with the MMR vaccine.
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Affiliation(s)
- Per Arne Parment
- Department of Communicable Disease Control and Prevention, Stockholm County Council, Stockholm, Sweden.
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Tosh PK, Kennedy RB, Vierkant RA, Jacobson RM, Poland GA. Correlation between rubella antibody levels and cytokine measures of cell-mediated immunity. Viral Immunol 2010; 22:451-6. [PMID: 19951182 DOI: 10.1089/vim.2009.0068] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Despite a safe and effective vaccine, endemic rubella remains a problem in developing countries. Isolated cases and outbreaks can occur in areas with high vaccine coverage. Individuals, especially pregnant women who remain unimmunized or do not seroconvert, are susceptible to infection and their infants are at risk for congenital rubella syndrome (CRS). Both humoral and cellular immune responses contribute to immune protection. Classically, immunity to rubella has been assessed through the detection of rubella-specific antibody titers. In this study we examined correlates of both humoral and cellular immunity in a large population of immunized young adults in Olmsted County, MN. We were unable to find any significant correlation between cytokine production after in-vitro rubella stimulation and serum antibody titers.
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Affiliation(s)
- Pritish K Tosh
- Mayo Vaccine Research Group, Mayo Clinic , Rochester, Minnesota 55905, USA
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Schmid DS, Jumaan AO. Impact of varicella vaccine on varicella-zoster virus dynamics. Clin Microbiol Rev 2010; 23:202-17. [PMID: 20065330 PMCID: PMC2806663 DOI: 10.1128/cmr.00031-09] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The licensure and recommendation of varicella vaccine in the mid-1990s in the United States have led to dramatic declines in varicella incidence and varicella-related deaths and hospitalizations. Varicella outbreaks remain common and occur increasingly in highly vaccinated populations. Breakthrough varicella in vaccinated individuals is characteristically mild, typically with fewer lesions that frequently do not progress to a vesicular stage. As such, the laboratory diagnosis of varicella has grown increasingly important, particularly in outbreak settings. In this review the impact of varicella vaccine on varicella-zoster virus (VZV) disease, arising complications in the effective diagnosis and monitoring of VZV transmission, and the relative strengths and limitations of currently available laboratory diagnostic techniques are all addressed. Since disease symptoms often resolve in outbreak settings before suitable test specimens can be obtained, the need to develop new diagnostic approaches that rely on alternative patient samples is also discussed.
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Affiliation(s)
- D Scott Schmid
- Herpesvirus Team and National VZV Laboratory, Measles, Mumps, Rubella, and Herpesvirus Laboratory Branch, Centers for Disease Control and Prevention, National Center for Immunizations and Respiratory Diseases, Division of Viral Diseases, Atlanta, Georgia 30333, USA.
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Mustafa MB, Arduino PG, Porter SR. Varicella zoster virus: review of its management. J Oral Pathol Med 2009; 38:673-88. [DOI: 10.1111/j.1600-0714.2009.00802.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Bonanni P, Breuer J, Gershon A, Gershon M, Hryniewicz W, Papaevangelou V, Rentier B, Rümke H, Sadzot-Delvaux C, Senterre J, Weil-Olivier C, Wutzler P. Varicella vaccination in Europe - taking the practical approach. BMC Med 2009; 7:26. [PMID: 19476611 PMCID: PMC2697173 DOI: 10.1186/1741-7015-7-26] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2009] [Accepted: 05/28/2009] [Indexed: 01/30/2023] Open
Abstract
Varicella is a common viral disease affecting almost the entire birth cohort. Although usually self-limiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete. In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all. In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella vaccines, as well as the optimal interval between two doses of measles, mumps, rubella and varicella vaccines). Assessment of the epidemiology of varicella in Europe and evidence for the effectiveness of varicella vaccination provides support for routine childhood programmes in Europe. Although European countries are faced with challenges or uncertainties that may have delayed implementation of a childhood vaccination programme, many of these concerns remain hypothetical and with new opportunities offered by combined measles, mumps, rubella and varicella vaccines, reassessment may be timely.
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Affiliation(s)
- Paolo Bonanni
- Department of Public Health, University of Florence, Florence, Italy
| | - Judith Breuer
- Skin Virus Laboratory, Centre for Cutaneous Research, St Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary College, London, UK
| | - Anne Gershon
- Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, USA
| | - Michael Gershon
- Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, USA
| | | | - Vana Papaevangelou
- Second Department of Pediatrics, University of Athens Medical School, "P & A Kyriakou" Children's Hospital, Athens, Greece
| | - Bernard Rentier
- Unit of Fundamental Virology and Immunology, GIGA-Research, B34 University of Liége, 4000 Liège, Belgium
| | - Hans Rümke
- Vaxinostics, University Vaccine Center Rotterdam Nijmegen, Rotterdam, the Netherlands
| | - Catherine Sadzot-Delvaux
- Unit of Fundamental Virology and Immunology, GIGA-Research, B34 University of Liége, 4000 Liège, Belgium
| | | | | | - Peter Wutzler
- Institute of Virology and Antiviral Therapy, Friedrich-Schiller University, Jena, Germany
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Marin M, Meissner HC, Seward JF. Varicella prevention in the United States: a review of successes and challenges. Pediatrics 2008; 122:e744-51. [PMID: 18762511 DOI: 10.1542/peds.2008-0567] [Citation(s) in RCA: 183] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE In 1995, the United States was the first country to introduce a universal 1-dose childhood varicella vaccination program. In 2006, the US varicella vaccine policy was changed to a routine 2-dose childhood program, with catchup vaccination for older children. The objective of this review was to summarize the US experience with the 1-dose varicella vaccination program, present the evidence considered for the policy change, and outline future challenges of the program. METHODS We conducted a review of publications identified by searching PubMed for the terms "varicella," "varicella vaccine," and "herpes zoster." The search was limited to US publications except for herpes zoster; we reviewed all published literature on herpes zoster incidence. RESULTS A single dose of varicella vaccine was 80% to 85% effective in preventing disease of any severity and >95% effective in preventing severe varicella and had an excellent safety profile. The vaccination program reduced disease incidence by 57% to 90%, hospitalizations by 75% to 88%, deaths by >74%, and direct inpatient and outpatient medical expenditures by 74%. The decline of cases plateaued between 2003 and 2006, and outbreaks continued to occur, even among highly vaccinated school populations. Compared with children who received 1 dose, in 1 clinical trial, 2-dose vaccine recipients developed in a larger proportion antibody titers that were more likely to protect against breakthrough disease and had a 3.3-fold lower risk for breakthrough disease and higher vaccine efficacy. Two studies showed no increase in overall herpes zoster incidence, whereas 2 others showed an increase. CONCLUSIONS A decade of varicella prevention in the United States has resulted in a dramatic decline in disease; however, even with high vaccination coverage, the effectiveness of 1 dose of vaccine did not generate sufficient population immunity to prevent community transmission. A 2-dose varicella vaccine schedule, therefore, was recommended for children in 2006. Data are inconclusive regarding an effect of the varicella vaccination program on herpes zoster epidemiology.
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Affiliation(s)
- Mona Marin
- Centers for Disease Control and Prevention, 1600 Clifton Rd, NE, MS A-47, Atlanta, GA 30333, USA.
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Macartney K, McIntyre P. Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults. Cochrane Database Syst Rev 2008:CD001833. [PMID: 18646079 DOI: 10.1002/14651858.cd001833.pub2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Live attenuated varicella vaccines for the prevention of varicella (chickenpox) has been demonstrated both in randomised controlled trials (RCTs) and in population-based immunisation programmes in countries such as the United States. However, many countries do not routinely immunise children against varicella, and exposures continue to occur. Although the disease is often mild, complications such as secondary bacterial infection, pneumonitis and encephalitis occur in about 1% of cases, usually leading to hospitalisation. The use of varicella vaccine in persons who have recently been exposed to the varicella zoster virus has been studied as a form of post-exposure prophylaxis (PEP). OBJECTIVES To assess the efficacy and safety of vaccines for use as PEP for the prevention of varicella in children and adults. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2008, Issue 1); MEDLINE (1966 to February 2008); and EMBASE (January 1990 to February 2008). SELECTION CRITERIA RCTs and quasi-RCTs of varicella vaccine for PEP compared with placebo or no intervention. The outcome measures were efficacy in prevention of clinical cases and/or laboratory-confirmed clinical cases and adverse effects following vaccination. DATA COLLECTION AND ANALYSIS Two review authors independently extracted and analysed data using Review Manager software. MAIN RESULTS Three studies involving 110 healthy children who were siblings of household contacts were identified as suitable for inclusion. The studies varied in quality, study design, vaccine used, and outcomes measured and, as such, were not suitable for meta-analysis. Overall, 13 out of 56 vaccine recipients (18%) developed varicella compared with 42 out of 54 placebo (or no vaccine) recipients (78%). Of the vaccine recipients who developed varicella, the majority only had mild disease (with less than 50 skin lesions). In the three studies, most subjects received PEP within three days following exposure; too few subjects were vaccinated four to five days post exposure to ascertain the efficacy of vaccine given more than three days after exposure. No included studies reported on adverse events following immunisation. AUTHORS' CONCLUSIONS These small trials suggest varicella vaccine administered within three days to children following household contact with a varicella case reduces infection rates and severity of cases. No RCTs for adolescents or adults were identified. However safety was not adequately addressed.
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Affiliation(s)
- Kristine Macartney
- National Centre for Immunisation Research (NCIRS), Children's Hospital at Westmead, Locked Bag 4001, Westmead, Sydney, NSW, Australia, 2145.
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Watson B. Humoral and cell-mediated immune responses in children and adults after 1 and 2 doses of varicella vaccine. J Infect Dis 2008; 197 Suppl 2:S143-6. [PMID: 18419388 DOI: 10.1086/522130] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Humoral and cell-mediated immune responses to varicella-zoster virus (VZV) have been evaluated after 1 and 2 doses of live attenuated varicella vaccine, Oka strain, in several studies. One dose of varicella vaccine, however, elicits detectable immune responses that are low and, in some cases, may be insufficient for complete protection against the virus after the normal decline in humoral and cell-mediated immunity with time. In contrast, immune responses after 2 doses are significantly higher and approximate the levels seen after natural disease. These investigations of vaccine-induced immunity suggest that 2 doses of VZV vaccine will better achieve the goals of the VZV vaccination program, by reducing the VZV burden of disease in childhood and preventing accumulation of young adults who are susceptible to or only partially protected from varicella.
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Affiliation(s)
- Barbara Watson
- Immunization Program Division of Disease Control, Philadelphia Department of Public Health, Philadelphia, Pennsylvania 19146, USA.
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Klein NP, Fireman B, Enright A, Ray P, Black S, Dekker CL. A role for genetics in the immune response to the varicella vaccine. Pediatr Infect Dis J 2007; 26:300-5. [PMID: 17414391 DOI: 10.1097/01.inf.0000257454.74513.07] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND A wide range in antibody titers has been found after immunization with the varicella vaccine, although the basis for these differences has not been described. METHODS To evaluate the contribution of a genetic component in the immune response to the varicella vaccine, concordance for six-week postimmunization antibody titers was evaluated among 248 biologic siblings who participated in varicella vaccine clinical trials by comparing all pairs of siblings (151 pairs) to all possible unrelated, nonsibling pairs created from within this same cohort (30,477 pairs). RESULTS Postimmunization antibody titers after 1 varicella vaccine dose were within the range observed historically among healthy vaccinees, with 85.4% of subjects having antibody responses greater than the approximate correlate of protection of 5 gpELISA units. Postimmunization antibody titers within sibling pairs clustered together more than or less than 10 gpELISA units when compared with within nonsibling pairs (P < 0.0001). Postimmunization titers within sibling pairs were also quantitatively closer together than were those within unrelated, nonsibling pairs (P = 0.022). The age-adjusted intraclass correlation coefficient indicated that the heritability of the varicella vaccine immune response is 45% (95% confidence interval of 15-75%). CONCLUSIONS Similarities in siblings' response to varicella vaccine are supportive of the hypothesis that genetic factors play a role in the antibody response to the varicella vaccine.
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Affiliation(s)
- Nicola P Klein
- Kaiser Permanente Vaccine Study Center and Division of Research, Oakland, CA 94612, USA.
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40
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Abstract
The disease burden of chickenpox to children has been described, and a lower force of neutralising antibody to varicella-zoster virus (VZV) than against measles, either after natural infection or after vaccination, has been reported. In the case of VZV, strong cell-mediated immunity may work efficiently to prevent the spread of the virus. The lower force of humoral antibody to VZV might be related to the occurrence of "breakthrough" varicella cases in a small portion of the vaccine recipients. Safety and high effectiveness of the varicella vaccine--approximately 85% effective for all diseases and 95-100% effective for moderate-to-severe diseases--have been reported. Vaccine-induced immunity persists for 10-20 years. However, concerns have been raised that universal immunisation in children may shift the susceptibility from children to adults, whose symptoms are usually moderate-to-severe. In addition, other concerns have been expressed that, due to lack of exposure to varicella in children, the elderly may develop zoster infections more frequently than before. A clear answer is difficult to give at present, although, for several reasons, such situations may be unlikely to occur.
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Affiliation(s)
- Michiaki Takahashi
- The Research Foundation for Microbial Diseases, Osaka University, Osaka, Japan
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41
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Nagasako EM, Johnson RW, Griffin DRJ, Elpern DJ, Dworkin RH. Geographic and racial aspects of herpes zoster. J Med Virol 2003; 70 Suppl 1:S20-3. [PMID: 12627482 DOI: 10.1002/jmv.10315] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Geographic and racial factors have been reported in studies of the epidemiology of varicella and herpes zoster. To clarify further these relationships, data from five multicenter clinical trials of the antiviral agent famciclovir were examined (total N = 2074). Non-Caucasian racial group and tropical region were each significantly associated with younger age at zoster onset. In analyses of the non-Caucasian subgroups, Black and Asian patients did not significantly differ in age or sex; however, Black and Asian patients from tropical regions had significantly younger mean ages at onset and greater rash duration at enrollment than those from temperate regions. Controlling for sex and rash duration at enrollment, both tropical region and non-Caucasian racial group were found to be independently associated with a younger age at zoster onset. These results suggest that racial group and geographic region may be independent factors associated with age at onset in patients with herpes zoster.
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Affiliation(s)
- Elna M Nagasako
- Washington University School of Medicine, St. Louis, Missouri, USA
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Abstract
Infections by VZV, the virus that causes chickenpox and herpes zoster, usually are diagnosed by the classic clinical presentations. In immunocompromised patients, however, the atypical presentation can make the diagnosis more challenging. Although varicella typically follows an uncomplicated course in children, adults and immunocompromised patients can develop complications involving several organs; some complications may be fatal. Prevention of disease with the vaccine is ideal. When varicella or zoster infection does occur, proper treatment should be initiated, depending on the age and immune status of the patient.
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Affiliation(s)
- T Minsue Chen
- Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
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43
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Jacquet A, Haumont M, Massaer M, Garcia L, Mazzu P, Daminet V, Grégoire D, Jacobs P, Bollen A. Immunogenicity of a recombinant varicella-zoster virus gE-IE63 fusion protein, a putative vaccine candidate against primary infection and zoster reactivation. Vaccine 2002; 20:1593-602. [PMID: 11858867 DOI: 10.1016/s0264-410x(01)00486-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The varicella-zoster virus (VZV) envelope glycoprotein E (gE) and immediate early protein 63 (IE63) are well known targets for specific humoral and cell-mediated immune responses during VZV infection and latency, respectively. The present study evaluated the immunogenicity of an engineered chimeric recombinant gE-IE63 (recgE-IE63) protein secreted from CHO cells, wherein a soluble form of gE, deleted of its anchor and cytoplasmic domains was fused to IE63. Guinea pig vaccinations with adjuvanted recgE-IE63 elicited a strong and specific humoral immune response directed to each counterpart. Sera from recgE-IE63-immunized animals neutralized cell-free VZV. This neutralizing capacity was dependent only on the recgE moiety as serum depletions on recgE-immobilized sepharose totally abolished VZV neutralization. The cell-mediated immune response induced by recgE-IE63 was evaluated in lymphoproliferation assays. An antigen-specific proliferative response was demonstrated after lymphocyte stimulation with recIE63 but not with recgE. We conclude that recombinant chimeric recgE-IE63 induced both humoral and cell-mediated immune responses and thus could constitute a putative subunit vaccine candidate against VZV primary infection and zoster reactivation.
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Affiliation(s)
- Alain Jacquet
- Department of Applied Genetics, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Rue des Professeurs Jeener et Brachet 12, B-6041 Gosselies, Belgium.
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Smith JG, Liu X, Kaufhold RM, Clair J, Caulfield MJ. Development and validation of a gamma interferon ELISPOT assay for quantitation of cellular immune responses to varicella-zoster virus. CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY 2001; 8:871-9. [PMID: 11527795 PMCID: PMC96163 DOI: 10.1128/cdli.8.5.871-879.2001] [Citation(s) in RCA: 136] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cell-mediated immunity appears to be critical for the prevention and control of varicella-zoster virus (VZV) infection and complications arising from zoster. Current assays of VZV-specific cell-mediated immunity are cumbersome or lack sensitivity. We have developed a gamma interferon ELISPOT assay that provides a direct measure of the number of T cells secreting a cytokine following stimulation with antigen. This assay is extremely sensitive and specific, with the ability to detect gamma interferon spot-forming cells (SFC) in the range of 10 to 1,000 SFC per million peripheral blood mononuclear cells (PBMCs). This assay has been validated by demonstrating the following: (i) the response detected is mediated almost entirely by CD4+ T cells, (ii) ELISPOT responses from fresh-frozen PBMCs are equivalent to those from freshly isolated cells, (iii) frozen PBMCs can be shipped on dry ice for up to 48 h without loss of activity, (iv) frozen PBMC samples can be stored in liquid nitrogen over long periods (>22 months) without any significant change in response, and (v) the numbers of ELISPOTs counted using a computer-based imaging system are equivalent to those counted by humans but have lower variability. The ability to use frozen cells is facilitated by the use of a recombinant nuclease (Benzonase) that can prevent cell clumping when samples are thawed. Frozen PBMC samples can be cycled through multiple changes in storage between liquid nitrogen and dry ice without any change in response being detected. This facilitates collection of samples at one site and testing performed at a remote location. This VZV ELISPOT assay provides a new versatile tool for monitoring cellular immune responses either during a herpes zoster disease outbreak or following vaccination.
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Affiliation(s)
- J G Smith
- Department of Virus and Cell Biology, Merck Research Labs, West Point, PA 19486, USA.
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45
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Abstract
This article reviews the history and development of live attenuated varicella vaccine from its early days in Japan to its widespread use throughout the world. The vaccine has proven extremely safe after immunization of as many as 10 million healthy children and adults in the United States alone. The vaccine is also highly immunogenic and offers close to 100% protection from severe chickenpox and 90% protection from illness. It is expected to have a major impact on the epidemiology of varicella and zoster in countries with high vaccine uptake.
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Affiliation(s)
- A A Gershon
- Department of Pediatrics, Columbia University College of Physicians & Surgeons, New York, New York, USA.
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46
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Massaer M, Haumont M, Garcia L, Mazzu L, Bollen A, Jacobs P, Jacquet A. Differential neutralizing antibody responses to varicella-zoster virus glycoproteins B and E following naked DNA immunization. Viral Immunol 1999; 12:227-36. [PMID: 10532651 DOI: 10.1089/vim.1999.12.227] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
The only available vaccine against varicella-zoster virus (VZV) consists of the VZV-Oka attenuated but persistent virus strain. Development of a safer, subunit vaccine is therefore desirable. In this prospect, nucleic acid vaccines, expressing truncated forms of VZV glycoproteins B (recgB) and E (recgE) from which the anchor and the cytoplasmic domains were deleted, were used to immunize mice. Vaccination with recgB encoding plasmid elicited a strong and specific humoral immune response. Total IgG and neutralizing titres were comparable to those previously obtained by vaccination with purified and adjuvanted native recgB. In contrast, mice immunization with recgE encoding plasmid only induced a very weak immune response whereas we previously showed that vaccination with adjuvanted native or denatured recgE protein led to high neutralizing titres. The weakness of the immune response induced by recgE-encoding plasmid depended neither on the deletion of the anchor domain in the gE gene nor on the animal model. Analysis of antibody isotypes produced by plasmid immunizations revealed a response slightly dominated by IgG2a. Taken together, the data indicate that a VZV subunit vaccine based on adjuvanted recombinant glycoprotein E is more promising than a nucleic acid-based vaccine strategy. As regards recgB, both vaccination approaches might be appropriate.
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Affiliation(s)
- M Massaer
- Applied Genetics, Université Libre de Bruxelles, Gosselies, Belgium
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47
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Welsh MD, Harper DR, Garcia-Valcarcel M, Fowler WJ, Aitken C, Jeffries DJ, Layton GT. Ability of yeast Ty-VLPs (virus-like particles) containing varicella-zoster virus (VZV)gE and assembly protein fragments to induce in vitro proliferation of human lymphocytes from VZV immune patients. J Med Virol 1999. [DOI: 10.1002/(sici)1096-9071(199909)59:1<78::aid-jmv13>3.0.co;2-p] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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48
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Wurtz R, Check IJ. Breakthrough varicella infection in a healthcare worker despite immunity after varicella vaccination. Infect Control Hosp Epidemiol 1999; 20:561-2. [PMID: 10466558 DOI: 10.1086/501670] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Although varicella vaccination is recommended for varicella-susceptible healthcare workers (HCWs), breakthrough infection after vaccination is not unusual, especially following household exposures. We report breakthrough varicella in a vaccinated HCW and review the data on breakthrough infection and concerns for the healthcare setting.
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Affiliation(s)
- R Wurtz
- Department of Medicine, Evanston Hospital, Illinois 60201, USA
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49
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Katial RK, Ratto-Kim S, Sitz KV, Moriarity R, Engler RJ. Varicella immunity: persistent serologic non-response to immunization. Ann Allergy Asthma Immunol 1999; 82:431-4. [PMID: 10353572 DOI: 10.1016/s1081-1206(10)62716-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
OBJECTIVE Varicella-zoster (VZV) infection is an occupational hazard for health care workers. The "gold standard" for assessing protection is a positive antibody titer. We present a case of persistent serologic non-responsiveness following VZV immunization and discuss a management strategy. METHODS A 29-year-old woman, immunocompetent pediatric resident was repeatedly removed from her clinical duties because of a negative history of chicken pox and the absence of a VZV antibody titer. She received a total of three doses of the VZV vaccine and continued to have a negative antibody titer as measured by a commercial ELISA assay (Wampole). Subsequently, she had three direct contacts with infectious children and did not develop clinical chicken pox. RESULTS A lymphocyte proliferation assay was performed using inactivated varicella vaccine and tetanus antigens. The patient's varicella and tetanus stimulation index (SI) were 46.5 and 42, respectively. The SI for the positive control (a patient recently recovered from a wild type infection) were 144 (varicella specific), and 114 (tetanus). The SI secondary to VZV antigens reported in the literature is 30.5 +/- 9.1. We reassessed the varicella antibody titer using more sensitive assays: fluorescent antibody to membrane antigen and latex agglutination. Both tests verified the presence of VZV specific IgG at a titer of 1:8 in our patient. CONCLUSION This case illustrates that in a subgroup of individuals the antibody response to VZV vaccine may be low despite an adequate cell-mediated response. Commercial VZV ELISA assays were designed to measure higher titers associated with natural infection rather than the lower titer induced by the vaccine. Repeated immunizations plus more sensitive measures of VZV-specific IgG should be used to validate protection rather than the current commonly utilized ELISA screening. Clinicians should be aware of the variability in VZV-specific antibody assays when assessing post VZV vaccine titers prior to determining protection in health care workers.
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Affiliation(s)
- R K Katial
- Department of Allergy and Immunology, Walter Reed Army Medical Center, Washington, DC 20307, USA
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50
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Habermehl P, Lignitz A, Knuf M, Schmitt HJ, Slaoui M, Zepp F. Cellular immune response of a varicella vaccine following simultaneous DTaP and VZV vaccination. Vaccine 1999; 17:669-74. [PMID: 10067672 DOI: 10.1016/s0264-410x(98)00249-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Chickenpox and zoster are an important cause of morbidity among children and adults. The ability of a new, thermostable vaccine to induce varicella-zoster-virus (VZV)-specific humoral and cell mediated immunity when given simultaneously with diphtheria-tetanus-acellular pertussis vaccine (DTaP) as a booster dose in the second year of life was investigated. METHODS A new, temperature stable varicella vaccine (OKA-strain, SB-Biologicals, Rixensart, Belgium) was given simultaneously with a booster dose of DTaP vaccine. VZV-specific humoral and cell-mediated immunity was studied in the first 27 out of 232 vaccinated children at 16-28 months of age, from blood samples drawn just before and six weeks after vaccination. VZV-specific antibody response, T-cell proliferation, cytokine production and expression of activation markers (CD25, HLADR) on T-cells were analyzed. RESULTS Vaccination resulted in a significant rise of VZV-specific serum IgG titers and in a strong VZV-specific T-cell response in all vaccinated infants. Analysis of the expression of activation marker revealed activation of both CD4+-T-helper- and CD8+-T-cells. CONCLUSIONS The varicella vaccine given simultaneously with DTaP produced strong B- and T-cell responses alike. This is the first report to show that CMI to VZV is conferred to young children by vaccination with a temperature stable VZV vaccine.
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Affiliation(s)
- P Habermehl
- Pediatric Immunology and Infectious Diseases, Johannes-Gutenberg-University, Mainz, Germany.
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