An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses.
BACKGROUND
A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI) H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP)-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e) of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses.


RESULTS
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.


CONCLUSIONS
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.
Zhao
Guangyu
G
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Lin
Yongping
Y
Du
Lanying
L
Guan
Jie
J
Sun
Shihui
S
Sui
Hongyan
H
Kou
Zhihua
Z
Chan
Chris Cs
CC
Guo
Yan
Y
Jiang
Shibo
S
Zheng
Bo-Jian
BJ
Zhou
Yusen
Y
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology*; D001835:Body Weight; D056738:Cross Protection; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000276:immunology; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D005620:Freund's Adjuvant; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins