A live-attenuated human-lamb rotavirus reassortant confers robust protective immunity in mice.

Group A rotavirus (RVA) is a leading cause of severe gastroenteritis and mortality in children under 5 years. Current vaccines rely on cell culture-attenuated human strains or human-animal reassortants. Here, we report the development of LG9, a monoreassortant rotavirus vaccine candidate engineered by replacing the VP7 gene of the Lanzhou lamb rotavirus(LLR,G10P[15]) with the human G9P[8] VP7 antigen (from clinical isolate HN-28). The LG9 strain exhibited robust genetic stability and replication kinetics in MA104 and Vero cells, matching parental LLR efficiency. Immunization of mice via oral or intraperitoneal routes induced high neutralizing antibody titers (post-boost titers increased >20-fold), with no adverse effects. Post-challenge, vaccinated mice showed good protection against diarrhea, fever and weight loss, contrasting with symptomatic outcomes in controls. These findings establish LG9 as a safe and immunogenic preclinical candidate while validating the LLR backbone as a versatile platform for developing multivalent live-attenuated rotavirus vaccines.