Immunogenicity and safety of a group B Streptococcus vaccine (GBS-AlpN) in pregnant women and their infants: Phase 2 multicentre, observer-blind, randomised, placebo-controlled study

Background: GBS-AlpN is a novel group B Streptococcus (GBS) maternal vaccine, based on the N-terminal domains of the alpha-like proteins (AlpNs) AlphaCN, RibN, Alp1N and Alp2/3N, which are responsible for 99% of invasive GBS strains. The aim of the study was to assess the safety and immunogenicity of GBS-AlpN in pregnant women receiving vaccination or placebo. <br/><br/>Methods: Phase 2 multicentre, observer-blind, randomised, placebo-controlled study conducted in 10 centres across South Africa, Denmark and the United Kingdom. Eligible participants were healthy pregnant women carrying a normal singleton at 21 weeks (+0 days) to 23 weeks (+6 days) gestational age (GA) at first vaccination. Participants were randomised via an electronic case report into five groups (2:2:2:2:1); randomisation was stratified by site. Participants received 0·5 mL GBS-AlpN (V) or normal saline placebo (P) intramuscularly at 22 (P), 26 (V) and 30 (V) weeks GA (Group 1); 22 (V), 26 (V) and 30 (P) weeks GA (Group 2); 22 (V), 26 (P) and 30 (V) weeks GA (Group 3); 22 (P), 26 (V) and 30 (P) weeks GA (Group 4); and 22 (P), 26 (P) and 30 (P) weeks GA (Group 5). All individuals (study staff and participants) were blinded, except those administering vaccines. The primary endpoint was the concentration of AlphaCN, RibN, Alp1N and Alp2/3N protein-specific IgG in cord blood or newborn blood obtained within 72 hours of birth. Safety endpoints were evaluated in the safety population; participants who received ≥1 vaccination, and their infants. Immunogenicity analyses included participants in the safety population who provided an evaluable sample following first GBS-AlpN or placebo. ClinicalTrials.Gov: NCT05154578; status: Closed.<br/><br/>Findings: between 17-Feb-2022 and 18-Oct-2023, 269 participants received ≥1 dose of GBS-AlpN or placebo (Group 1 PVV [n=61]; Group 2 VVP [n=59]; Group 3 VPV [n=59]; Group 4 PVP [n=60]; Group 5 PPP [n=30]). The highest serum IgG concentrations at birth were observed in Group 1, followed by the other two dose vaccine groups (Groups 2 and 3). Lower IgG concentrations were observed in Group 4, although these were still ≥21-fold higher than placebo. Treatment-emergent adverse events were reported by 56 (91·8%) maternal participants in Group 1, 54 (91·5%) in Group 2; 57 (96·6%) in Group 3; 56 (93·3%) in Group 4 and 26 (86·7%) in Group 5; most events were mild–moderate. Nine infant fatalities were reported; none were considered related to vaccination. <br/><br/>Interpretation: GBS-AlpN was safe and immunogenic when administered to pregnant women, supporting its progression to phase 3 trials, with a flexible two-dose schedule allowing 4–8-week dosing intervals.<br/>