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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

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
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
Background: a new formulation of the live-attenuated varicella vaccine Varilrix (GSK) produced without human serum albumin (HSA) was developed to minimize a theoretical risk of transmission of infectious diseases. A previous study showed that the vaccine was immunologically non-inferior to the HSA-containing vaccine and well-tolerated in toddlers; low-grade fever was numerically higher in children receiving the vaccine without HSA, but the study lacked power to conclude on this difference.Methods: in this phase III, double-blind, multi-center study, healthy 12–23-month-olds were randomized (1:1) to receive two doses of the varicella vaccine without (Var-HSA group) or with HSA (Var + HSA group) at days 0 and 42. The primary objective compared safety of the vaccines in terms of incidence of fever > 39.0 °C in the 15-day period post-first vaccination. The objective was considered met if the upper limit of the 95% confidence interval for the between-group difference in the incidence of fever > 39.0 °C was ≤5% (Var-HSA group minus Var + HSA group). Safety, reactogenicity and immune responses were evaluated.Results: six hundred fifteen children in the Var-HSA group and 616 in the Var + HSA group received ≥1 vaccination. Fever > 39.0 °C was reported in 3.9 and 5.2% of participants in the Var-HSA and Var + HSA groups, with a between-group difference of − 1.29 (95% confidence interval: − 3.72–1.08); therefore, the primary objective was achieved. Fever rates post-each dose and the incidence of solicited local and general adverse events (AEs) were comparable between groups. Unsolicited AEs were reported for 43.9 and 36.5% of children in the Var-HSA group and 45.8 and 36.0% of children in the Var + HSA group, during 43 days post-dose 1 and 2, respectively. Serious AEs occurred in 2.1% (group Var-HSA) and 2.4% (group Var + HSA) of children, throughout the study. In a sub-cohort of 364 children, all had anti-varicella-zoster virus antibody concentrations ≥50 mIU/mL post-dose 2; comparable geometric mean concentrations were observed between the groups.Conclusions: the varicella vaccine formulated without HSA did not induce higher rates of fever during the 15 day-post-vaccination period, as compared with the original HSA-containing vaccine. The two vaccines displayed similar safety and immunogenicity profiles in toddlers.
1471-2431
Faust, Saul
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Le Roy, Maguelone
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Pancharoen, Chitsanu
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Rodriguez Weber, Miguel Angel
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Cathie, Katrina
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Behre, Ulrich
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Bernatoniene, Jolanta
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Snape, Matthew
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Helm, Klaus
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Medina Pech, Carlos Eduardo
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Henry, Ouzama
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Baccarini, Carmen
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Povey, Michael
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Gillard, Paul
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Faust, Saul
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Le Roy, Maguelone
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Pancharoen, Chitsanu
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Rodriguez Weber, Miguel Angel
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Cathie, Katrina
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Behre, Ulrich
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Bernatoniene, Jolanta
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Snape, Matthew
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Helm, Klaus
eb641473-c8f2-4b16-8fdd-3f0df5242ea8
Medina Pech, Carlos Eduardo
52242761-dcc5-448f-aa5b-791b48665daa
Henry, Ouzama
152e4dfc-eee5-41d5-978d-684c6be7632e
Baccarini, Carmen
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Povey, Michael
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Gillard, Paul
a4954737-7331-4235-9f53-0799a0df0caa

Faust, Saul, Le Roy, Maguelone, Pancharoen, Chitsanu, Rodriguez Weber, Miguel Angel, Cathie, Katrina, Behre, Ulrich, Bernatoniene, Jolanta, Snape, Matthew, Helm, Klaus, Medina Pech, Carlos Eduardo, Henry, Ouzama, Baccarini, Carmen, Povey, Michael and Gillard, Paul (2019) 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. BMC Pediatrics, 19. (doi:10.1186/s12887-019-1425-7).

Record type: Article

Abstract

Background: a new formulation of the live-attenuated varicella vaccine Varilrix (GSK) produced without human serum albumin (HSA) was developed to minimize a theoretical risk of transmission of infectious diseases. A previous study showed that the vaccine was immunologically non-inferior to the HSA-containing vaccine and well-tolerated in toddlers; low-grade fever was numerically higher in children receiving the vaccine without HSA, but the study lacked power to conclude on this difference.Methods: in this phase III, double-blind, multi-center study, healthy 12–23-month-olds were randomized (1:1) to receive two doses of the varicella vaccine without (Var-HSA group) or with HSA (Var + HSA group) at days 0 and 42. The primary objective compared safety of the vaccines in terms of incidence of fever > 39.0 °C in the 15-day period post-first vaccination. The objective was considered met if the upper limit of the 95% confidence interval for the between-group difference in the incidence of fever > 39.0 °C was ≤5% (Var-HSA group minus Var + HSA group). Safety, reactogenicity and immune responses were evaluated.Results: six hundred fifteen children in the Var-HSA group and 616 in the Var + HSA group received ≥1 vaccination. Fever > 39.0 °C was reported in 3.9 and 5.2% of participants in the Var-HSA and Var + HSA groups, with a between-group difference of − 1.29 (95% confidence interval: − 3.72–1.08); therefore, the primary objective was achieved. Fever rates post-each dose and the incidence of solicited local and general adverse events (AEs) were comparable between groups. Unsolicited AEs were reported for 43.9 and 36.5% of children in the Var-HSA group and 45.8 and 36.0% of children in the Var + HSA group, during 43 days post-dose 1 and 2, respectively. Serious AEs occurred in 2.1% (group Var-HSA) and 2.4% (group Var + HSA) of children, throughout the study. In a sub-cohort of 364 children, all had anti-varicella-zoster virus antibody concentrations ≥50 mIU/mL post-dose 2; comparable geometric mean concentrations were observed between the groups.Conclusions: the varicella vaccine formulated without HSA did not induce higher rates of fever during the 15 day-post-vaccination period, as compared with the original HSA-containing vaccine. The two vaccines displayed similar safety and immunogenicity profiles in toddlers.

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Accepted/In Press date: 31 January 2019
e-pub ahead of print date: 7 February 2019

Identifiers

Local EPrints ID: 428490
URI: https://eprints.soton.ac.uk/id/eprint/428490
ISSN: 1471-2431
PURE UUID: 01caf9f7-7aea-4f98-be1e-62e20a292b4f
ORCID for Saul Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 28 Feb 2019 17:30
Last modified: 20 Jul 2019 00:54

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Contributors

Author: Saul Faust ORCID iD
Author: Maguelone Le Roy
Author: Chitsanu Pancharoen
Author: Miguel Angel Rodriguez Weber
Author: Katrina Cathie
Author: Ulrich Behre
Author: Jolanta Bernatoniene
Author: Matthew Snape
Author: Klaus Helm
Author: Carlos Eduardo Medina Pech
Author: Ouzama Henry
Author: Carmen Baccarini
Author: Michael Povey
Author: Paul Gillard

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