Influenza A virus (IAV), a deadly zoonotic pathogen, occasionally
cross-species transmission among humans, swine and avian. The ectodomain
of matrix protein 2 (M2e) is highly conserved in IAV and has been widely
concerned in the development of universal influenza vaccines. Due to low
immunogenicity, multi-copy M2e are usually displayed on the surface of
nanoparticles to constitute universal nanovaccines. Here, we report that
the permutation of the M2e affects the immune effect of the nanovaccine.
Three M2e derived from humans, swine and avian IAV were inserted into
the C-terminal of the Cap protein of porcine circovirus type 2 (PCV2) to
form self-assembled nanovaccine. Immunoprotective effects of different
M2e arrangements were explored in mice. Results showed that the M2e
closest to the surface of nanoparticle induced the most efficient
protection against IAV derived from corresponding species. The results
will help in the development of more effective universal influenza
vaccines, especially for specific species.