A protective immune response in mice to viral components other than hemagglutinin in a live influenza A virus vaccine model.
Previously, we generated influenza A viruses that possess chimeric type (A/B) hemagglutinins (HA), in which immunogenic regions of type A HA were replaced with those of type B HA, and showed that these viruses were attenuated in mice (J. Virol. 77 (2003) 8031). Here, we intranasally immunized mice with these viruses and then challenged them with a wild-type A virus to assess a protective immune response to viral components other than HA in the form of a live virus. All immunized mice survived challenge with a lethal dose of wild-type virus; none or a limited amount of virus, if any, was recovered from nasal turbinates or lungs of the mice 3 days post-challenge. These results provide direct evidence that immune responses to viral components other than HA confer protection against influenza A virus infection in a mouse model, suggesting the usefulness of live vaccines for viruses that have undergone antigenic drift with respect to HA, or for viruses with heterosubtypic HAs.
Horimoto
Taisuke
T
Department of Microbiology and Immunology, University of Tokyo, Tokyo, Japan. horimoto@ims.u-tokyo.ac.jp
Takada
Ayato
A
Iwatsuki-Horimoto
Kiyoko
K
Kawaoka
Yoshihiro
Y
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009296:Nasal Cavity / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated