Maternal antibody interference contributes to reduced rotavirus vaccine efficacy in developing countries

Rotavirus (RV) vaccine efficacy is significantly reduced in lower- and middle-income countries (LMICs) compared to high-income countries. This review summarizes current research into the mechanisms behind this phenomenon, with a particular focus on the evidence that maternal antibody (matAb) interference is a contributing factor to this disparity. All RV vaccines currently in use are orally administered, live-attenuated virus vaccines that replicate in the infant gut, which leaves their efficacy potentially impacted by both placentally transferred immunoglobulin G (IgG) and mucosal IgA Abs conferred via breast milk. Observational studies of cohorts in LMICs demonstrated an inverse correlation between matAb titers, both in serum and breast milk, and infant responses to RV vaccination. However, a causal link between maternal humoral immunity and reduced RV vaccine efficacy in infants has yet to be definitively established, partially due to limitations in current animal models of RV disease. The characteristics of Abs mediating interference and the mechanism(s) involved have yet to be determined, and these may differ from mechanisms of matAb interference for parenterally administered vaccines due to the contribution of mucosal immunity conferred via breast milk. Increased vaccine doses and later age of vaccine administration have been strategies applied to overcome matAb interference, but these approaches are difficult to safely implement in the setting of RV vaccination in LMICs. Ultimately, the development of relevant animal models of matAb interference is needed to determine what alternative approaches or vaccine designs can safely and effectively overcome matAb interference of infant RV vaccination.