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Background  Rotavirus is the leading cause of severe dehydrating diarrhea in young children and the inner capsid protein VP6 is a potential vaccine candidate that can induce cross-protective immune responses against different Rotavirus strains. The use of ferritin nanoparticles as the scaffold of the antigen can improve the immunogenicity of the subunit vaccines and provide broader protection. We here present a non-live and self-assemble recombinant rotavirus VP6–ferritin (rVP6–ferritin) nanoparticle vaccine.    Results  The rVP6–ferritin nanoparticles were expressed in  E. coli  and self-assembled to uniform spherical structure which similar to ferritin, and oral administration of them induced efficient humoral and mucosal immunogenicity in mice. The nanoparticles were further transgenically expressed in the milk of mice, and pup mice breastfed by transgenic rVP6–ferritin mothers had strongly induced immunogenicity and—compared to pups breastfed by wild type mothers—the proportion of rotavirus challenged pups with diarrhea symptoms, the duration and intensity of the diarrhea, and the deleterious effects on overall growth resulting from the diarrhea were all significantly reduced.    Conclusions  These results suggest that this recombinant VP6–ferritin nanoparticle vaccine can efficiently prevent the death and malnutrition induced by the rotavirus infection in infants and is a promising candidate vaccine for rotavirus.    Electronic supplementary material  The online version of this article (10.1186/s12951-019-0446-6) contains supplementary material, which is available to authorized users.

A milk-based self-assemble rotavirus VP6–ferritin nanoparticle vaccine elicited protection against the viral infection