Development of high-yield influenza A virus vaccine viruses

• Published in: Nature communications 2015-09, Vol.6 (1), p.8148-8148, Article 8148
• Main Authors: Ping, Jihui, Lopes, Tiago J.S., Nidom, Chairul A., Ghedin, Elodie, Macken, Catherine A., Fitch, Adam, Imai, Masaki, Maher, Eileen A., Neumann, Gabriele, Kawaoka, Yoshihiro
• Format: Article
• Language: English
• Subjects: 13/106; 13/109; 38/23; 42/40; 631/154/309/2144; 631/250/24/590; 631/326/596/1578; 64/60; Animals; Backbone; Base Sequence; Cell culture; Cercopithecus aethiops; Dogs; Eggs; Exo-a-sialidase; HEK293 Cells; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinins; Humanities and Social Sciences; Humans; Influenza; Influenza A; Influenza A virus - genetics; Influenza A virus - immunology; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - genetics; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H5N1 Subtype - genetics; Influenza A Virus, H5N1 Subtype - immunology; Influenza A Virus, H7N9 Subtype - genetics; Influenza A Virus, H7N9 Subtype - immunology; Influenza Vaccines - biosynthesis; Influenza Vaccines - immunology; Kidneys; Madin Darby Canine Kidney Cells; Molecular Sequence Data; multidisciplinary; Mutation; Neuraminidase - genetics; Pandemics; Poultry; Propagation; Regulatory sequences; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Screens; Vaccine development; Vaccines; Vero Cells; Viruses; Yield
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9148

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. The availability of high-yield virus strains remains an important bottleneck in the rapid production of influenza vaccines. Here, the authors report the development of influenza A vaccine backbone that improves the virus yield of various seasonal and pandemic influenza vaccine strains in cell culture.