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Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial

BACKGROUND: GSK’s varicella vaccine contains human serum albumin (HSA) which is used to stabilize the virus and prevent immunogens from adhering to the injection vial walls. However, because HSA is derived from human blood, there is a theoretical risk that it might contain infectious agents which co...

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Autores principales: Prymula, Roman, Simko, Robert, Povey, Michael, Kulcsar, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712494/
https://www.ncbi.nlm.nih.gov/pubmed/26762528
http://dx.doi.org/10.1186/s12887-016-0546-5
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author Prymula, Roman
Simko, Robert
Povey, Michael
Kulcsar, Andrea
author_facet Prymula, Roman
Simko, Robert
Povey, Michael
Kulcsar, Andrea
author_sort Prymula, Roman
collection PubMed
description BACKGROUND: GSK’s varicella vaccine contains human serum albumin (HSA) which is used to stabilize the virus and prevent immunogens from adhering to the injection vial walls. However, because HSA is derived from human blood, there is a theoretical risk that it might contain infectious agents which could be unsafe for humans. Given this concern, a study was undertaken to compare the immunogenicity and safety of a new formulation without HSA with the currently licensed varicella vaccine in the Czech Republic and Hungary. METHODS: Healthy children aged 11–21 months received two doses of the varicella vaccine either with or without HSA. Antibody titres against varicella-zoster virus (anti-VZV) were measured 42 days after each dose, using an immunofluorescence assay (IFA, cut-off = 4dilution(−1)) and enzyme linked immunosorbent assay (ELISA, cut-off = 25 mIU/ml). Solicited local symptoms were recorded during a 4-day post-vaccination follow-up period; solicited general and unsolicited symptoms were recorded during a 43-day post-vaccination follow-up period and serious adverse event (SAEs) were recorded throughout the study. RESULTS: Of 244 children (mean age = 15.2 months [SD = 3.2]) vaccinated in the study, 233 (vaccine without HSA N = 117; vaccine containing HSA N = 116) formed the according-to-protocol immunogenicity cohort. Observed seroconversion/seroresponse rates were >98 and 100 %, 42 days after doses 1 and 2, respectively. The rates were within the same range in both groups, irrespective of the testing assay. The varicella vaccine without HSA was non-inferior to the licensed vaccine in terms of anti-VZV antibody Geometric Mean Titre/Concentration ratio (1.12 [95 % CI:0.86–1.46] by IFA; 1.12 [95 % CI:0.93–1.33] by ELISA) approximately six weeks after the first dose of the 2-dose vaccination course. The incidence of solicited and unsolicited symptoms was similar after both vaccines; low-grade fever was numerically higher after the first dose of the varicella vaccine without HSA. Seven SAEs were reported, none of which were fatal or considered to be vaccine-related. CONCLUSIONS: The first dose of a new varicella vaccine without HSA was immunologically non-inferior to the licensed varicella vaccine. After two doses, both vaccines had acceptable safety profiles in children aged 11–21 months in the Czech Republic and Hungary. TRIAL REGISTRATION: NCT00568334, registered on 5 December 2007 (www.clinicaltrials.gov).
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spelling pubmed-47124942016-01-15 Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial Prymula, Roman Simko, Robert Povey, Michael Kulcsar, Andrea BMC Pediatr Research Article BACKGROUND: GSK’s varicella vaccine contains human serum albumin (HSA) which is used to stabilize the virus and prevent immunogens from adhering to the injection vial walls. However, because HSA is derived from human blood, there is a theoretical risk that it might contain infectious agents which could be unsafe for humans. Given this concern, a study was undertaken to compare the immunogenicity and safety of a new formulation without HSA with the currently licensed varicella vaccine in the Czech Republic and Hungary. METHODS: Healthy children aged 11–21 months received two doses of the varicella vaccine either with or without HSA. Antibody titres against varicella-zoster virus (anti-VZV) were measured 42 days after each dose, using an immunofluorescence assay (IFA, cut-off = 4dilution(−1)) and enzyme linked immunosorbent assay (ELISA, cut-off = 25 mIU/ml). Solicited local symptoms were recorded during a 4-day post-vaccination follow-up period; solicited general and unsolicited symptoms were recorded during a 43-day post-vaccination follow-up period and serious adverse event (SAEs) were recorded throughout the study. RESULTS: Of 244 children (mean age = 15.2 months [SD = 3.2]) vaccinated in the study, 233 (vaccine without HSA N = 117; vaccine containing HSA N = 116) formed the according-to-protocol immunogenicity cohort. Observed seroconversion/seroresponse rates were >98 and 100 %, 42 days after doses 1 and 2, respectively. The rates were within the same range in both groups, irrespective of the testing assay. The varicella vaccine without HSA was non-inferior to the licensed vaccine in terms of anti-VZV antibody Geometric Mean Titre/Concentration ratio (1.12 [95 % CI:0.86–1.46] by IFA; 1.12 [95 % CI:0.93–1.33] by ELISA) approximately six weeks after the first dose of the 2-dose vaccination course. The incidence of solicited and unsolicited symptoms was similar after both vaccines; low-grade fever was numerically higher after the first dose of the varicella vaccine without HSA. Seven SAEs were reported, none of which were fatal or considered to be vaccine-related. CONCLUSIONS: The first dose of a new varicella vaccine without HSA was immunologically non-inferior to the licensed varicella vaccine. After two doses, both vaccines had acceptable safety profiles in children aged 11–21 months in the Czech Republic and Hungary. TRIAL REGISTRATION: NCT00568334, registered on 5 December 2007 (www.clinicaltrials.gov). BioMed Central 2016-01-13 /pmc/articles/PMC4712494/ /pubmed/26762528 http://dx.doi.org/10.1186/s12887-016-0546-5 Text en © Prymula et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Prymula, Roman
Simko, Robert
Povey, Michael
Kulcsar, Andrea
Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial
title Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial
title_full Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial
title_fullStr Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial
title_full_unstemmed Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial
title_short Varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial
title_sort varicella vaccine without human serum albumin versus licensed varicella vaccine in children during the second year of life: a randomized, double-blind, non-inferiority trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712494/
https://www.ncbi.nlm.nih.gov/pubmed/26762528
http://dx.doi.org/10.1186/s12887-016-0546-5
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