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

Vaccine. 2020 Apr 3;38(16):3227-3234. doi: 10.1016/j.vaccine.2020.02.085. Epub 2020 Mar 10.

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.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial
  • Female
  • Humans
  • Immunogenicity, Vaccine*
  • Streptococcal Vaccines / adverse effects
  • Streptococcal Vaccines / immunology*
  • Streptococcus agalactiae
  • Vaccination
  • Vaccines, Conjugate

Substances

  • Antibodies, Bacterial
  • Streptococcal Vaccines
  • Vaccines, Conjugate

Associated data

  • ClinicalTrials.gov/NCT02270944