An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus

Leung, Ho-Chuen; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Zhao, Han-Jun; Cheung, Chung-Yan; Ng, Fai; Huang, Jian-Dong; Zheng, Bo-Jian

Although early treatments with oseltamivir and peramivir were effective, 3, 8, 9 drug-resistant mutants of the virus were found soon after the patients received the anti-influenza therapy. 10 Candidates of inactivated virus vaccines and virus-like particle (VLP) vaccines of H7N9 virus have been reported. 11 However, the use of inactivated virus vaccines or VLP may not provide protection against mutated or reassorted influenza virus. In fact, a surveillance study has suggested that the novel influenza A H7N9 virus is a new reassortant of several influenza viruses, including H7, N9, and H9N2. 6 Therefore, development of universal influenza vaccines is an attractive goal for scientists around the world. In this regard, the ectodomain of matrix protein 2 (M2e) of influenza viruses may be a promising target for the development of a universal influenza vaccine. This is because M2e is relatively conserved in different subtypes of influenza virus, 12, 13 and animal experiments have demonstrated that M2e vaccination can provide cross-protection against infection with different subtypes of influenza virus. H5N1-M2e-specific antibodies could react with different subtypes of influenza virus, such as H5N2, H9N2, H7N7, and H11N6. 14 Various M2e-based vaccines have been developed, such as recombinant protein vaccines, [15] [16] [17] [18] plasmid DNA vaccines, 19 and peptide vaccines. 20, 21 In our previous studies, we constructed a tetrameric H5N1-M2e vaccine candidate and demonstrated that it could provide cross-protection against lethal infections with different clades of H5N1 and 2009 pandemic H1N1 viruses. 20, 21 In this study, we extend our investigation to evaluate cross-protection of H5N1-M2e against lethal infection by the novel avian influenza A H7N9 virus in mice.