title: Development of high-yield influenza B virus vaccine viruses.
abstract: The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.
authors.affiliation: Department of Pathobiological Sciences, Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711.
authors.forename: Jihui
authors.initials: J
authors.lastname: Ping
authors.affiliation: Department of Pathobiological Sciences, Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711.|Division of Virology, Department of Microbiology and Immunology, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Tiago J S
authors.initials: TJ
authors.lastname: Lopes
authors.affiliation: Department of Pathobiological Sciences, Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.affiliation: Department of Pathobiological Sciences, Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711; kawaokay@svm.vetmed.wisc.edu.|Division of Virology, Department of Microbiology and Immunology, University of Tokyo, Tokyo 108-8639, Japan.|International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage; D002645:Chickens; D002522:Chlorocebus aethiops; D004285:Dogs; D015723:Gene Library; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000235:genetics; D009981:Influenza B virus / Q000235:genetics*; D007252:Influenza Vaccines; D007251:Influenza, Human / Q000517:prevention & control; D061985:Madin Darby Canine Kidney Cells; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012367:RNA, Viral / Q000235:genetics; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D012367:RNA, Viral; D009439:Neuraminidase
keywords: Victoria lineage; Yamagata lineage; high-yield; influenza B virus; vaccine