Bach, F.; Sigal, G. B.; Wohlstadter, J.; Brown, R.; Dunn, G.; Ngo, T.; Ngo, B.; Demos, C.; Musinguzi, K.; Nankya, F.; Kakuru, A.; Sbarra, A.; Dorsey, G.; Kamya, M. R.; Takahashi, S.; Jagannathan, P.

Vaccine immunogenicity is consistently lower in low-income countries than in high-income settings, yet the factors driving this disparity remain incompletely understood. Using multiplexed electrochemiluminescence serology, we measured IgG and IgA responses to Expanded Program on Immunization (EPI) vaccines and common childhood viral infections in 89 Ugandan infants. We integrated detailed parasitological surveillance and maternal clinical data to examine how P. falciparum infection history, concurrent parasitemia, maternal gravidity, and early-life viral exposures shaped serological profiles. We found that infants mounted robust responses to most EPI vaccines, but critical gaps in protection persisted for diphtheria, measles and rubella. Children born to primigravid mothers had lower antibody levels at 8 weeks of age, independent of placental malaria and only partially explained by maternal age. Contrary to expectation, cumulative P. falciparum exposure was positively associated with antibody concentrations to diphtheria and varicella, and concurrent parasitemia was positively correlated with responses to multiple antigens. Early seroconversion to rhinovirus C was associated with higher polio IgA and rotavirus IgG concentrations at 24 weeks. Together, these findings suggest that common microbial exposures during infancy, including respiratory viruses and P. falciparum may positively modulate vaccine responsiveness.