title: Identification of Influenza A/PR/8/34 Donor Viruses Imparting High Hemagglutinin Yields to Candidate Vaccine Viruses in Eggs.
abstract: One of the important lessons learned from the 2009 H1N1 pandemic is that a high yield influenza vaccine virus is essential for efficient and timely production of pandemic vaccines in eggs. The current seasonal and pre-pandemic vaccine viruses are generated either by classical reassortment or reverse genetics. Both approaches utilize a high growth virus, generally A/Puerto Rico/8/1934 (PR8), as the donor of all or most of the internal genes, and the wild type virus recommended for inclusion in the vaccine to contribute the hemagglutinin (HA) and neuraminidase (NA) genes encoding the surface glycoproteins. As a result of extensive adaptation through sequential egg passaging, PR8 viruses with different gene sequences and high growth properties have been selected at different laboratories in past decades. The effect of these related but distinct internal PR8 genes on the growth of vaccine viruses in eggs has not been examined previously. Here, we use reverse genetics to analyze systematically the growth and HA antigen yield of reassortant viruses with 3 different PR8 backbones. A panel of 9 different HA/NA gene pairs in combination with each of the 3 different lineages of PR8 internal genes (27 reassortant viruses) was generated to evaluate their performance. Virus and HA yield assays showed that the PR8 internal genes influence HA yields in most subtypes. Although no single PR8 internal gene set outperformed the others in all candidate vaccine viruses, a combination of specific PR8 backbone with individual HA/NA pairs demonstrated improved HA yield and consequently the speed of vaccine production. These findings may be important both for production of seasonal vaccines and for a rapid global vaccine response during a pandemic.
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Adam
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Chen
authors.affiliation: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Emily
authors.initials: E
authors.lastname: Winne
authors.affiliation: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Wanda
authors.initials: W
authors.lastname: Santana
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Maureen G
authors.initials: MG
authors.lastname: Metcalfe
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Guaniri
authors.initials: G
authors.lastname: Mateu-Petit
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Callie
authors.initials: C
authors.lastname: Ridenour
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: M Jaber
authors.initials: MJ
authors.lastname: Hossain
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Villanueva
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
authors.affiliation: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Tracie L
authors.initials: TL
authors.lastname: Williams
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.affiliation: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Barr
authors.affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Ruben O
authors.initials: RO
authors.lastname: Donis
mesh_terms: D000818:Animals; D002645:Chickens; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D007252:Influenza Vaccines / Q000276:immunology*; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010063:Ovum / Q000821:virology; D016865:Reassortant Viruses / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D006388:Hemagglutinins; D007252:Influenza Vaccines; D014764:Viral Proteins; D009439:Neuraminidase