An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses

Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum) adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses.These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.The re-emergence of H5N1 highly pathogenic avian influenza (HPAI) in 2003 has caused 262 fatal cases among a total of 442 infected individuals [1]. Therefore, there is an urgent need to develop safe and effective antiviral strategies for the prevention of any future pandemic of H5N1 HPAI [2,3], among which vaccination is still the most effective means to prevent influenza A virus infection. Due to current vaccine technologies facing annual problems with vaccine-strain matching, some conserved antigens of influenza A virus become promising target for the development of influenza vaccines with broad cross-protection.In comparison with other surface proteins of H5N1 viruses, matrix protein 2 (M2) is the most conserved. The native M2 protein exists as a homotetramer formed by two disulfide linked dimers, with each monomer consisting of 97 amino acids [4,5]. The 24-amino-acid extracellular domain of M2 protein (M2e) is remarkably conserved across influenza A subtypes [6]. Passively transferred anti-M2 monoclonal antibodies (mAbs) accelerated lung viral clearance [7], and mAbs recognizing the N-terminus highly conserved epitope in M2e protected mice from lethal influenza A virus challenge [8], implying that M2, in particular M2e