Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in pregnant women and their infants: Results from a randomized placebo-controlled phase II trial

Abstract

Background: This study evaluated the safety and immunogenicity of an investigational trivalent group B streptococcus (GBS) vaccine in US pregnant women, transplacental serotype-specific antibody transfer and persistence in infants, and serotype-specific antibodies in breast milk. Methods: This randomized, observer-blind, placebo-controlled trial administered one dose of trivalent GBS vaccine (n = 49) or placebo (n = 26) to healthy pregnant 18–40-year-old women at 240/7–346/7 weeks’ gestation. Women were enrolled from March 2014 to August 2015. Safety follow-up continued through postpartum day 180. Primary immunogenicity objectives were to evaluate serotype Ia/Ib/III-specific immunoglobulin G (IgG) levels in sera from women on day 1 (pre-vaccination), day 31, delivery and postpartum days 42 and 90, and from infants at birth (cord blood), days 42 and 90. Antibody transfer ratios (cord blood/maternal sera at delivery) and serotype-specific secretory immunoglobulin A (sIgA) and IgG in breast milk after delivery and on postpartum days 42 and 90 were evaluated. The planned sample size was not based on statistical assumptions for this descriptive study. Results: Baseline characteristics were similar between groups. Serious adverse events were reported for 16% of GBS-vaccinated women and 15% of their infants, and 15% of placebo recipients and 12% of their infants; none were fatal or deemed vaccine-related. Serotype-specific IgG geometric mean concentrations (GMCs) were 13–23-fold higher in vaccine vs placebo recipients on day 31 and persisted until postpartum day 90. Median antibody concentrations were substantially higher in women with detectable pre-vaccination antibody concentrations. Antibody transfer ratios in the vaccine group were 0.62–0.82. Infant IgG GMCs and breast milk sIgA GMCs were higher in the vaccine vs the placebo group at all timepoints. Conclusions: Maternal immunization with the trivalent GBS vaccine in US women had a favorable safety profile, elicited antibodies that were transplacentally transferred and persisted in infants for a minimum of 3 months. Clinical trial registration: Clinicaltrials.gov, NCT02046148