Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2.
Matix protein 2 (M2) is a transmembrane protein of influenza type A virus. It contains a 23 aa long ectodomain (M2e) that is highly conserved amongst human influenza type A viruses. M2e-specific antibodies have been shown to restrict virus growth in vitro and in vivo and thus have the potential of providing cross-reactive resistance to influenza type A virus infection. We attempted to induce M2e-specific protection with synthetic multiple antigen peptide (MAP) constructs that contained covalently linked M2e- and Th-determinant peptides. Mice, vaccinated twice by the intranasal (i.n.) route with adjuvanted M2e-MAPs exhibited significant resistance to virus replication in all sites of the respiratory tract. Compared to mice primed by two consecutive heterosubtypic infections, resistance was of similar strength in nasal and tracheal tissue but lower in pulmonary tissue. Importantly, the protection in M2e-MAP- and infection-immunized mice appeared to be mediated by distinct immune mechanisms. This suggests that stronger protection may be achievable by combining both protective activities.
Immunology Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4268, USA.
Krystyna
K
Mozdzanowska
JinQi
J
Feng
Mark
M
Eid
Goran
G
Kragol
Mare
M
Cudic
Laszlo
L
Otvos
Walter
W
Gerhard
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology* / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009666:Nose / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D017433:Protein Structure, Secondary; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology*; D000086082:Viroporin Proteins
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins