A biepitope, adjuvant-free, self-assembled influenza nanovaccine provides cross-protection against H3N2 and H1N1 viruses in mice.

Currently, the incorporation of multiple epitopes into vaccines is more desirable than the incorporation of a single antigen for universal influenza vaccine development. However, epitopes induce poor immune responses. Although the use of adjuvants can overcome this obstacle, it may raise new problems. Effective antigen delivery vehicles that can function as both antigen carriers and intrinsic adjuvants are highly desired for vaccine development. Here, we report a biepitope nanovaccine that provides complete protection in mice against H3N2 virus as well as partial protection against H1N1 virus. This vaccine (3MCD-f) consists of two conserved epitopes (matrix protein 2 ectodomain (M2e) and CDhelix), and these epitopes were presented on the surface of ferritin in a sequential tandem format. Subcutaneous immunization with 3MCD-f in the absence of adjuvant induces robust humoral and cellular immune responses. These results provide a proof of concept for the 3MCD-f nanovaccine that might be an ideal candidate for future influenza pandemics. © Tsinghua University Press 2022.