Abstract
Maternal antibodies are transferred transplacentally to fetuses and then through lactation to infants to protect them whilst their own immune system is still immature. However, these maternal antibodies also suppress neonatal B-cell responses, thereby impairing vaccine efficacy and leaving infants potentially vulnerable to life-threatening pathogens, such as rotaviruses. Currently available rotavirus vaccines are composed of live-attenuated viral strains administered to infants orally at 6-8 weeks old. Although high concentrations of maternal antibodies correlate with poor production of antibodies following vaccination (i.e., seroconversion), the immunological basis of this interference is unknown. To investigate the underlying mechanisms, we here developed a mouse model of neonatal oral rotavirus vaccination, in which vaccination only fails to induce seroconversion if maternal antibodies are present. Such antibodies are shown to block vaccine replication, while faster maternal antibody waning is observed in vaccinated compared to unvaccinated pups. FcγRIIB deletion does not overcome interference in pups, although pup IgG levels increase when maternal antibody titers are very low. Our findings show that maternal antibody-mediated vaccine clearance is a key mechanism of interference with oral rotavirus vaccines, with a minor role for FcγRIIB in neonatal IgG responses.