Influenza A viruses possessing type B hemagglutinin and neuraminidase: potential as vaccine components.
A licensed live attenuated influenza vaccine is available as a trivalent mixture of types A (H1N1 and H3N2) and B vaccine viruses. Thus, interference among these viruses could restrict their replication, affecting vaccine efficacy. One approach to overcoming this potential problem is to use a chimeric virus possessing type B hemagglutinin (HA) and neuraminidase (NA) in a type A vaccine virus background. We previously generated a type A virus possessing a chimeric HA in which the entire ectodomain of the type A HA molecule was replaced with that of the type B HA, and showed that this virus protected mice from challenge by a wild-type B virus. In the study described here, we generated type A/B chimeric viruses carrying not only the chimeric (A/B) HA, but also the full-length type B NA instead of the type A NA, resulting in (A/B) HA/NA chimeric viruses possessing type B HA and NA ectodomains in the background of a type A virus. These (A/B) HA/NA chimeric viruses were attenuated in both cell culture and mice as compared with the wild-type A virus. Our findings may allow an effective live influenza vaccine to be produced from a single master strain, providing a model for the design of future live influenza vaccines.
Horimoto
Taisuke
T
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA. horimoto@ims.u-tokyo.ac.jp
Iwatsuki-Horimoto
Kiyoko
K
Hatta
Masato
M
Kawaoka
Yoshihiro
Y
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D002460:Cell Line; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D009981:Influenza B virus / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009296:Nasal Cavity / Q000821:virology; D009439:Neuraminidase / Q000235:genetics*; D011995:Recombination, Genetic; D014611:Vaccination; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D009439:Neuraminidase