Development of high-yield influenza A virus vaccine viruses.
Vaccination is one of the most cost-effective ways to prevent infection. Influenza vaccines propagated in cultured cells are approved for use in humans, but their yields are often suboptimal. Here, we screened A/Puerto Rico/8/34 (PR8) virus mutant libraries to develop vaccine backbones (defined here as the six viral RNA segments not encoding haemagglutinin and neuraminidase) that support high yield in cell culture. We also tested mutations in the coding and regulatory regions of the virus, and chimeric haemagglutinin and neuraminidase genes. A combination of high-yield mutations from these screens led to a PR8 backbone that improved the titres of H1N1, H3N2, H5N1 and H7N9 vaccine viruses in African green monkey kidney and Madin-Darby canine kidney cells. This PR8 backbone also improves titres in embryonated chicken eggs, a common propagation system for influenza viruses. This PR8 vaccine backbone thus represents an advance in seasonal and pandemic influenza vaccine development.
Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.
Jihui
J
Ping
Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.|Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Tiago J S
TJS
Lopes
Avian Influenza-Zoonosis Research Center, Airlangga University, Surabaya 60115, Indonesia.
Chairul A
CA
Nidom
Department of Biology, New York University, New York, New York 10003 USA.|Department of Computational &Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 USA.
Elodie
E
Ghedin
Bioinformatics Institute, University of Auckland, Auckland 1010, New Zealand.
Catherine A
CA
Macken
Department of Computational &Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 USA.
Adam
A
Fitch
Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.
Masaki
M
Imai
Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.
Eileen A
EA
Maher
Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.
Gabriele
G
Neumann
Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.|Division of Virology, Department of Microbiology and Immunology and International Research Center for Infectious Diseases, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Yoshihiro
Y
Kawaoka
D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D004285:Dogs; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000096:biosynthesis* / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics; D014709:Vero Cells
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009439:Neuraminidase