Antigen-Presenting, Self-Assembled Protein Nanobarrels as an Adjuvant-Free Vaccine Platform against Influenza Virus

Although naturally occurring, self-assembled protein nanoarchitectures have been utilized as antigen-delivery carriers, and the inability of such carriers to elicit immunogenicity requires additional use of strong adjuvants. Here, we report an immunogenic Brucella outer membrane protein BP26-derived nanoarchitecture displaying the influenza extracellular domain of matrix protein-2 (M2e) as a vaccine platform against influenza virus. Genetic engineering of a monomeric BP26 containing four or eight tandem repeats of M2e resulted in a hollow barrel-shaped nanoarchitecture (BP26-M2e nanobarrel). Immunization with BP26-M2e nanobarrels induced a strong M2e-specific humoral immune response in vivo that was much greater than that of a physical mixture of soluble M2e and BP26, with or without the use of an alum adjuvant. An anti-M2e antibody generated by BP26-M2e nanobarrel-immunized mice specifically bound to influenza virus-infected cells. Furthermore, in viral challenge tests, BP26-M2e nanobarrels effectively protected mice from influenza virus infection-associated death, even without the use of a conventional adjuvant. A mechanism study revealed that both M2e-specific antibody-dependent cellular cytotoxicity and T cell responses are involved in the vaccine efficacy of BP26-M2e nanobarrels. These findings suggest that the BP26-based nanobarrel developed here represents a versatile vaccine platform that can be used against various viral infections.