Safety and immunogenicity of fully liquid and lyophilized formulations of an investigational trivalent group B streptococcus vaccine in healthy non-pregnant women: Results from a randomized comparative phase II trial

Abstract

Background: We evaluated the safety and immunogenicity of liquid and lyophilized formulations of an investigational trivalent group B streptococcus (GBS) vaccine in non-pregnant women and assessed the formulations' equivalence in terms of serotype-specific immune response.

Methods: This phase II, randomized, comparative, observer-blind trial enrolled healthy non-pregnant women 18-40 years of age. Women received a single dose of fully liquid (n = 529) or lyophilized (n = 521) trivalent GBS vaccine on day 1. Safety assessments were performed up to day 181 (study termination). Serotype Ia/Ib/III-specific immunoglobulin G (IgG) antibodies were measured in sera from women on day 1 (pre-vaccination) and day 31. Equivalence between the two formulations was demonstrated if the two-sided 95% confidence interval (CI) for the ratio (liquid/lyophilized) of the geometric mean concentrations (GMCs) on day 31 was contained in a (0.5, 2.0) interval for each serotype.

Results: Solicited and unsolicited adverse events were reported at similar rates for both formulations. Serious adverse events were reported for six (1.1%) liquid GBS and nine (1.7%) lyophilized GBS vaccinated women, none of which were considered related to vaccination or fatal. On day 31, serotype-specific IgG concentrations were 8-16-fold higher than on day 1 in both groups. Equivalence of the liquid to the lyophilized formulation 30 days post-vaccination was demonstrated as the 95% CIs of the GMC ratios were within the pre-specified interval for the three serotypes: GMC ratios were 1.02 (95% CI: 0.79, 1.32) for serotype Ia, 0.93 (0.71, 1.21) for serotype Ib and 0.99 (0.76, 1.30) for serotype III.

Conclusions: Both formulations of the investigational trivalent GBS vaccine had favorable safety profiles and induced similar GBS serotype-specific antibody concentrations. This study demonstrated that the fully liquid formulation was equivalent to the lyophilized formulation in healthy non-pregnant women in terms of immunogenicity for all three serotypes.

Clinical trials registration: NCT02270944.

Keywords: Group B streptococcus; Immunogenicity; Liquid; Lyophilized; Maternal immunization; Safety.

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ZB, ML, OH, BC, AK, AD and CS are employees of the GSK group of companies. ML, OH, BC and AK hold shares in the GSK group of companies. For the work under consideration, GLR, PVD, CV and MAI declare that their institutions have been compensated by the GSK group of companies for the costs involved in the conduct of the study, JdH declares funding from Novartis Vaccine for industry sponsored clinical trial and JP declares personal fees from the GSK group of companies for service as principal investigator. Outside the submitted work, GLR declares personal fees from the GSK group of companies, Osivax, Virometix and Ablynx for consulting activities, PVD declares that his institution has received grants from the GSK group of companies, Pfizer, Sanofi, Merck, Takeda, Baxter, CanSino China, Osivax, Themis, Johnson & Johnson, Abbott, the Bill & Melinda Gates foundation, the Flemish government and the European Union; SB declares that she is consultant statistician for the GSK group of companies. JB and CJ have nothing to disclose.

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