One-step preparation of a self-assembled bioconjugate nanovaccine against .

Brucellosis, caused by , is a severe zoonosis, and the current live attenuated vaccine cannot be used in humans due to major safety risks. Although polysaccharide antigens can be used to prepare the vaccine, their lower immunogenicity limits them from producing efficient and broad protection. In this study, we produced a high-performance bioconjugate nanovaccine against different species of by introducing a self-assembly nanoparticle platform and an O-linked glycosylation system into serotype O:9, which has an -polysaccharide composed of the same unit as . After successfully preparing the vaccine and confirming its stability, we subsequently demonstrated the safety of the vaccine in mice by high-dose immunization. Then, by a series of mouse experiments, we found that the nanovaccine greatly promoted antibody responses. In particular, the increase of IgG2a was more obvious than that of IgG1. Most importantly, this nanovaccine could provide cross-protection against , , and strains by lethal dose challenged models, and could improve the clearance of , the most common pathogenic species in human brucellosis, by non-lethal dose infection. Overall, for the first time, we biocoupled polysaccharide antigens with nano carriers to prepare a vaccine, which showed pronounced and extensive protective effects in mice. Thus, we provided a potential candidate vaccine and a new direction for vaccine design.