The study investigated the kinetics of rotavirus-specific IgG and IgA antibodies in mothers and infants in Malawi to determine the optimal timing of a booster dose of Rotarix vaccine. They collected longitudinal sera from 84 infants at five time points (January 2021–October 2023) and cross-sectional samples from 798 individuals aged 0–86 years (December 2022–June 2024). Before the first dose of vaccine, infants who seroconverted had lower median maternal IgG levels (5745 IU/ml) compared to seronegatives (9689.8 IU/ml; p=0.015), with low levels increasing the odds of seroconversion by more than 5-fold (OR=5.8; 95% CI: 1.6–24.2; p=0.012). The model showed that the mean IgG concentration in non-seroconverters fell below the threshold at 6.2 months, at the population level at 8.4 months, which is related to the peak of severe rotavirus gastroenteritis at 9 months. Serum IgA levels peaked at 9 months and were associated with a decline in disease incidence between 9 and 17 months. The findings recommend a booster dose between 6 and 8 months of age, when maternal antibodies are low and disease risk is high, to increase vaccine immunogenicity in low- and middle-income countries.