Intranasal administration of a synthetic peptide vaccine encapsulated in liposome together with an anti-CD40 antibody induces protective immunity against influenza A virus in mice.
Mucosal immunity is critical for protection from viral infections. We attempted to activate mucosal cytotoxic T lymphocytes (CTLs) specific for influenza A virus nucleoprotein (NP) which play an important role in protective immunity. It has been shown that dendritic cells (DCs) activated by signaling via CD40-CD40 ligand (CD40L) interaction are required for the differentiation of naive CD8(+) T cells into antigen-specific CTLs in a non-mucosal environment. We herein inoculated mice intranasally with an anti-CD40 monoclonal antibody (anti-CD40 mAb) and NP366-374 peptide, corresponding to a CTL epitope on NP, encapsulated in liposome (liposomal NP366-374) to induce protective CTL responses against influenza A virus. Intranasal but not subcutaneous immunization with liposomal NP366-374 effectively induced mucosal immunity to reduce virus replication in the lung, suggesting that anti-CD40 mAb also functioned as a mucosal adjuvant. Interestingly, neither MHC class I- nor class II-deficient mice immunized intranasally with these materials were resistant to the infection. Since anti-CD40 mAb was considered to help replace CD4(+) T cells, another help of CD4(+) T cells are presumably required for the induction of CTL activity in the lung. This approach may prove promising for developing vaccines to induce mucosal CTL responses, and seems to highlight differences between mucosal and non-mucosal immunity.
Ninomiya
Ai
A
Department of Disease Control, Hokkaido University Graduate School of Veterinary Medicine, Sapporo 060-0818, Japan.
Ogasawara
Kazumasa
K
Kajino
Kiichi
K
Takada
Ayato
A
Kida
Hiroshi
H
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D018928:Immunity, Mucosal / Q000276:immunology; D007115:Immunization Schedule; D009980:Influenza A virus / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007700:Kinetics; D008081:Liposomes / Q000008:administration & dosage; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000008:administration & dosage* / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014758:Viral Core Proteins / Q000008:administration & dosage* / Q000276:immunology; D014779:Virus Replication; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; D008081:Liposomes; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D001613:beta 2-Microglobulin; C102366:nucleoprotein (366-374), influenza virus