posted on 2021-06-11, 16:12authored bySukmo Kang, Yujin Kim, Yumi Shin, Ji-Joon Song, Sangyong Jon
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.