Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1.
Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that crossreacted with human and avian M2 sequences and produced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A.
Tompkins
Stephen Mark
SM
Food and Drug Administration, Bethesda, Maryland, USA. tompkins@vet.uga.edu
Zhao
Zi-Shan
ZS
Lo
Chia-Yun
CY
Misplon
Julia A
JA
Liu
Teresa
T
Ye
Zhiping
Z
Hogan
Robert J
RJ
Wu
Zhengqi
Z
Benton
Kimberly A
KA
Tumpey
Terrence M
TM
Epstein
Suzanne L
SL
D000256:Adenoviridae / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D005260:Female; D005814:Genes, Viral; D005822:Genetic Vectors / Q000008:administration & dosage / Q000378:metabolism; D007115:Immunization Schedule; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007473:Ion Channels / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000086082:Viroporin Proteins
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D007473:Ion Channels; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins