Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization.
DNA immunization offers a novel means to induce cellular immunity in a population with a heterogeneous genetic background. An immunorecessive cytotoxic T-lymphocyte (CTL) epitope in influenza virus nucleoprotein (NP), residues 218 to 226, was identified when mice were immunized with a plasmid DNA encoding a full-length mutant NP in which the anchor residues for the immunodominant NP147-155 epitope were altered. Mice immunized with wild-type or mutant NP DNA were protected from lethal cross-strain virus challenge, and the protection could be adoptively transferred by immune splenocytes, indicating the role of cell-mediated immunity in the protection. DNA immunization is capable of eliciting protective cellular immunity against both immunodominant and immunorecessive CTL epitopes in the hierarchy seen with virus infection.
Fu
T M
TM
Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Friedman
A
A
Ulmer
J B
JB
Liu
M A
MA
Donnelly
J J
JJ
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology*; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins