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...

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Bibliographic Details
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:	eng
Subjects:	Animals Backbone Base Sequence Cell culture Cercopithecus aethiops Dogs Eggs Exo-a-sialidase HEK293 Cells Hemagglutinin Glycoproteins, Influenza Virus - genetics Hemagglutinins 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 Mutation Neuraminidase - genetics Pandemics Poultry Propagation Regulatory sequences Ribonucleic acid RNA Screens Vaccine development Vaccines Vero Cells Viruses Yield
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Summary:	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.
ISSN:	2041-1723 2041-1723