Abstract

Rotavirus is a leading cause of pediatric diarrheal mortality. The rotavirus outer capsid consists of VP7 and VP4 proteins, which, respectively, determine viral G and P type and are primary targets of neutralizing antibodies. To elucidate VP7-specific neutralizing antibody responses, we engineered monoreassortant rotaviruses each containing a human VP7 segment from a sequenced clinical specimen or a vaccine strain in an identical genetic background. We quantified replication and neutralization of engineered viruses using sera from infants vaccinated with monovalent ROTARIX or multivalent RotaTeq vaccines. Immunization with RotaTeq induced broader neutralizing antibody responses than ROTARIX. Inclusion of a single dose of RotaTeq in the schedule enhanced G-type neutralization breadth of vaccinated infant sera. Cell type-specific differences in infectivity, replication, and neutralization were detected for some monoreassortant viruses. These findings suggest that rotavirus VP7, independent of VP4, can contribute to cell tropism and the breadth of vaccine-elicited neutralizing antibody responses.

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