Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1

Stephen Mark Tompkins; Zi-Shan Zhao; Chia-Yun Lo; Julia A Misplon; Teresa Liu; Zhiping Ye; Robert J Hogan; Zhengqi Wu; Kimberly A Benton; Terrence M Tumpey; Suzanne L Epstein

doi:10.3201/eid1303.061125

Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1

Emerg Infect Dis. 2007 Mar;13(3):426-35. doi: 10.3201/eid1303.061125.

Authors

Stephen Mark Tompkins¹, Zi-Shan Zhao, Chia-Yun Lo, Julia A Misplon, Teresa Liu, Zhiping Ye, Robert J Hogan, Zhengqi Wu, Kimberly A Benton, Terrence M Tumpey, Suzanne L Epstein

Affiliation

¹ Food and Drug Administration, Bethesda, Maryland, USA. [email protected]

Abstract

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.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adenoviridae / metabolism
Amino Acid Sequence
Animals
Antibodies, Viral / blood
Antibodies, Viral / immunology
Cross Reactions / immunology
Drug Evaluation, Preclinical
Female
Genes, Viral
Genetic Vectors / administration & dosage
Genetic Vectors / metabolism
Immunization Schedule
Influenza A Virus, H5N1 Subtype / immunology*
Influenza Vaccines / administration & dosage*
Influenza Vaccines / immunology
Injections, Intramuscular
Injections, Intraperitoneal
Ion Channels / immunology*
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Orthomyxoviridae Infections / blood
Orthomyxoviridae Infections / prevention & control*
Recombinant Proteins / biosynthesis
Recombinant Proteins / immunology
Sequence Alignment
T-Lymphocytes / immunology
Vaccination*
Vaccines, DNA / immunology
Vaccines, Synthetic / genetics
Vaccines, Synthetic / immunology
Viral Matrix Proteins / genetics
Viral Matrix Proteins / immunology*
Viral Matrix Proteins / metabolism

Substances

Antibodies, Viral
Influenza Vaccines
Ion Channels
M2 protein, Influenza A virus
Recombinant Proteins
Vaccines, DNA
Vaccines, Synthetic
Viral Matrix Proteins