A randomized prospective study of neonatal hepatitis B vaccine immunogenicity in The Gambia and Papua New Guinea

Background: Protection of newborns from infection can be achieved through maternal or vaccine-induced antibodies, but the factors influencing vaccine protection (correlate of protection) and subsequent infant immunity remain insufficiently understood. Further investigation is essential to optimize early-life vaccination strategies. Objective: We sought to evaluate the impact of timing and sequence of hepatitis B vaccine (HBV) and Bacille Calmette-Guérin (BCG) vaccine within the first week of life on infant HBV immunogenicity and its relationship with maternal antibodies. Methods: This was an exploratory analysis of a US National Institutes of Health-supported prospective, randomized study of systems biology signatures predictive of HBV immunogenicity in 2 geographically distinct cohorts in The Gambia (GAM; N = 720) and Papua New Guinea (PNG, N = 101) (clinicaltrials.gov NCT03246230). Healthy, hepatitis B surface antigen (anti-HBs)-negative mothers and their infants were enrolled and randomized into 4 vaccine groups: HBV alone, BCG alone, HBV + BCG, or no vaccination (delayed until no later than day of life [DOL]7). Blood samples were collected at birth (DOL0) and on a randomly assigned day (either DOL1, DOL3, or DOL7) with a maximum of 2 blood draws in the first week of life per ethics approval. All infants received catch-up vaccination within DOL7 and the recommended oral polio vaccine within 10 days of birth. Additional blood samples were collected at DOL30 and DOL128 to measure anti-HBs titers and assess immunogenicity. Results: = .019, respectively). Conclusions: This study demonstrates the feasibility of conducting large-scale neonatal immunogenicity studies in resource-constrained settings. Our observations underscore the importance of vaccine timing and maternal antibodies in shaping early-life vaccine-induced immunogenicity, offering valuable insights for neonatal vaccination schedules.