Reasonable permutation of M2e
enhances the effect of universal influenza nanovaccine
Running title: Optimize M2e universal influenza nanovaccine
Peiyang Ding1, Gaping Zhang1, 2,
Yumei Chen1, Hongliang Liu1, 2,
Yunchao Liu2, Rui Jia2, Yanwei
Wang1, 2, Ge Li2, Aiping
Wang1*
1School of Life Sciences, Zhengzhou University,
Zhengzhou 450001, China
2Henan Zhongze Biological Engineering Co., Ltd.,
Zhengzhou 450002, China
*To whom correspondence should be addressed:
Aiping Wang E-mail: pingaw@126.com
Tel.: +86-037167739345; Fax: +86-037163558998
Address: School of Life Sciences, Zhengzhou University, Zhengzhou
450001, China
Abstract
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 multi-copy M2e
from different species are usually displayed on the surface of
nanoparticles to improve immunogenicity and constitute universal IAV
nanovaccines. In our previous study, three M2e were inserted into the
C-terminal of Cap protein of porcine circovirus type 2 (PCV2) to form a
universal nanovaccine that protects PCV2 and different subtypes of IAV.
Howerer, M2e adopts at least two converted conformations, and the
intermolecular linker of M2e enhances the conformational instability,
which limits the recognition of B cell receptors and production of
high-level antibodies. Here, we report that the permutation of the M2e
affects immune effect of nanovaccines. Three M2e derived from humans,
swine and avian IAV were inserted into the C-terminal of the Cap protein
to form nanovaccines. 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 to
develop more effective universal IAV and PCV2 bivalent nano-vaccines, as
well as universal IAV vaccines for specific species.
Keywords: influenza A virus; porcine circovirus type 2; M2e;
universal; nanovaccine; permutation