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A randomized prospective study of neonatal hepatitis B vaccine immunogenicity in The Gambia and Papua New Guinea
Joann Diray-Arce1,2,3, Caitlin Syphurs1, Annmarie Hoch1
1Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, Mass.
Insights
Neonatal vaccine timing impacts infant immunity. This study explored hepatitis B vaccine (HBV) and BCG vaccine sequences, finding that maternal antibodies and vaccination schedules influence early infant immune responses.
Area of Science:
- Neonatal immunology
- Vaccine development
- Infectious disease prevention
Background:
- Infant protection from infection relies on maternal or vaccine-induced antibodies.
- Factors influencing vaccine protection and infant immunity require further study for optimized early-life vaccination.
Purpose of the Study:
- To evaluate the impact of hepatitis B vaccine (HBV) and Bacille Calmette-Guérin (BCG) vaccine timing and sequence on infant HBV immunogenicity.
- To investigate the relationship between infant HBV immunogenicity and maternal antibodies.
Main Methods:
- Prospective, randomized study in The Gambia and Papua New Guinea involving healthy mothers and infants.
- Infants were randomized into four groups: HBV alone, BCG alone, HBV + BCG, or delayed vaccination.
- Blood samples collected at birth and during the first week of life, plus at days 30 and 128, to measure anti-HBs titers.
Main Results:
- Maternal and neonatal anti-HBs titers were strongly correlated.
- Early anti-HBs titers predicted later titers at day 30 but not day 128.
- Specific vaccine timings showed varied impacts on anti-HBs titers in different cohorts, with BCG at birth and HBV at day 7 showing higher day 30 titers in The Gambia.
Conclusions:
- The study highlights the feasibility of large-scale neonatal immunogenicity studies in resource-limited settings.
- Vaccine timing and maternal antibodies are crucial factors in shaping early-life vaccine-induced immunogenicity.
- Findings provide valuable insights for optimizing neonatal vaccination schedules.
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:
Demographic and clinical characteristics were balanced across vaccine groups, suggesting successful randomization in both cohorts. Similar infant growth trajectories and longitudinal anti-HBs titer trends were observed across all vaccine groups in both cohorts over the first 128 days of life. Maternal and neonatal baseline anti-HBs titers were strongly correlated (GAM: r = 0.98; PNG: r = 0.99). DOL0 titers predicted DOL30 titers (GAM: R 2 = 0.56; PNG: R 2 = 0.945) but not DOL128 titers. Exploratory pairwise comparisons showed that Gambian infants receiving BCG at birth and HBV at DOL7 had higher DOL30 titers than those vaccinated with HBV at DOL1 (Wilcoxon P = .046), whereas in PNG, infants in the HBV + BCG group and the delayed group had higher DOL128 titers than those in the HBV group (Wilcoxon P = .046; Wilcoxon P = .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.
