Maternal malaria and early-life infections shape humoral immunity to P. falciparum in infants

Placental malaria may negatively impact acquisition of immunity to malaria in infants. To study the effect of maternal antibodies on early-life infections, a birth cohort of infants were enrolled in a prospective observational study in Busia, Uganda. We measured P. falciparum-specific antibody responses to 19 P. falciparum antigens and tetanus toxoid in 183 infants using a Luminex multiplex bead array. We also assessed the frequency and phenotype of peripheral T follicular helper cells and B cells using flow cytometry. Placental malaria and lower gestational age adversely impacted antibody transfer overall. Maternal antibodies present in cord blood were not associated with protection in the first year of life, and neither was maternal malaria status. Infants generated antibodies against P. falciparum antigens in response to infection, but these were also not associated with protection, only exposure. Interestingly, infections in the first six months of life correlated with decreased levels of antibodies to P. falciparum antigen at one year of age. Early-life infections were not clearly associated with circulating follicular T cell or B cell phenotypic composition. These data suggest the infant antibody response has little, if any, impact on preventing clinical malaria or patent parasitemia in the first year of life.