EVALUATING IMMUNOGENICITY OF A HEPATITIS B BIRTH DOSE VACCINE IN DEMOCRATIC REPUBLIC OF CONGO AND OF MEASLES VACCINATION IN THE CONTEXT OF MALARIA INFECTION IN KENYA

Childhood infections with hepatitis B virus (HBV) and measles cause significant morbidity and mortality in sub-Saharan Africa, despite both viruses having highly effective vaccines. In this dissertation, we aimed to (1) characterize the immunogenicity of adding a birth-dose of HBV vaccine (HepB-BD) to the existing 3-dose HBV vaccine schedule (HepB3) in Kinshasa, Democratic Republic of Congo among HBV-unexposed and HBV-exposed infants and (2) assess measles antibody response among infants living in areas of high and low malaria transmission in Western Kenya. In the first aim, we compared the proportion of HBV-unexposed infants who had protective antibodies against HBV after HepB3 versus HepB3 plus HepB-BD and compared the proportion of infants with protective antibodies after HepB3 plus HepB-BD between HBV-exposed and HBV-unexposed infants. We found that a similar proportion of HBV-unexposed infants who received HepB3 with and without HepB-BD had protective antibody levels at 12 months (92.9% (95% CI: 75.7%-98.2%) vs. 85.7% (67.5%-94.5%), respectively). Notably, a high proportion of HBV-exposed infants had protective antibody levels at 12 months (96.9% (81.2%-99.6%)). These findings emphasize the importance of HepB-BD among HBV-exposed infants and demonstrate a need for future research studies into the impact of HepB-BD among HBV-unexposed infants. In the second aim, we compared measles antibody levels after vaccination at 9 months of age and examined how the proportions of infants in each response category changed through 24 months of age between infants living in areas of high versus low malaria transmission. Among infants without pre-vaccine measles exposure, more infants living in the low malaria study site were in the highest category of antibody response at 10-12 months compared with infants living in the high malaria study site (41.5% vs. 23.9%, chi-square p=0.1). Most infants moved to the high antibody category throughout the duration of the study, and this change in categories did not differ between study sites. Surprisingly, 30.6% of infants had evidence of measles exposure prior to vaccination, suggesting that more measles may have been circulating in these populations than was appreciated at the time. Future studies should investigate potentially lower vaccine effectiveness in areas with high malaria transmission.