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

Abstract

BackgroundGSK’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.MethodsHealthy 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.ResultsOf 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.ConclusionsThe 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 registrationNCT00568334, registered on 5 December 2007 (www.clinicaltrials.gov).

Safety and immunogenicity of a varicella vaccine without human serum albumin (HSA) versus a HSA-containing formulation administered in the second year of life: a phase III, double-blind, randomized study

“…In the current study, although a slight increase in the incidence of fever > 38.0 °C related to vaccination was observed for the varicella vaccine without HSA, exploratory analyses showed that the incidence of fever of any severity was similar between the two groups in the 15-day period following first vaccination. Similar fever rates were found for low grade fever (> 38.0 °C) between the two vaccine groups for the 8-day post-first vaccination, in contrast with previous observations [6]. No increase in the incidence of fever was observed after the second dose and data related to the intensity, onset, duration and outcome of the reported fever cases post-each vaccination did not indicate any clinically significant difference between the two vaccines.…”

“…The immunogenicity of the two vaccines following each vaccination was comparable, in line with previously reported results [6]. Following first vaccination, point-estimates for seroresponse rates were lower in the group receiving the vaccine without HSA, but the 95% CIs were overlapping and the study was not powered to assess any statistical difference for immunogenicity results.…”

“…A previous trial indicated a slight numerical increase in the incidence of fever ≥37.5 °C for the varicella vaccine without HSA, but the statistical significance of the difference could not be evaluated, as the study was not powered to detect differences in terms of fever between groups [6]. Our study included a larger number of children of the same age (1231 vs 244 in the previous study) and was powered to assess any statistically-significant increase in rate of fever > 39.0 °C in the 15-day period post-first vaccination.…”

“…In a previous study in children 11–21 months of age conducted in two European countries, the immunogenicity of a first dose of varicella vaccine without HSA was demonstrated to be non-inferior to that of the HSA-containing varicella vaccine and both formulations showed acceptable safety profiles [6]. Unexpectedly, after the first vaccination, a slightly higher rate of fever ≥37.5 °C, but not in fever > 39.0 °C, was observed in children receiving the vaccine produced without HSA (28.1–95% CI: 20.3–37.0%) as compared to the HSA-containing varicella vaccine (18.0–95% CI: 11.7–26.0%) [6].…”

Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice

“…However, we also detected aggregate formation, especially in electron microscope images. We added human serum albumin (<0.02%) to the final product to increase the stability, to prevent viral particles from adhering to the injection vial walls, and efficacy of the vaccine candidate (Prymula, Simko, Povey, & Kulcsar, 2016). Besides, when we assess residual Vero host cell protein and DNA level in each vaccine dose, it was found that the protein level was <4ng and DNA was absent in the dose.…”