Extending the Stalk Enhances Immunogenicity of the Influenza Virus Neuraminidase

Journal of Virology
Felix BroeckerPeter Palese

Abstract

Influenza viruses express two surface glycoproteins, the hemagglutinin (HA) and the neuraminidase (NA). Anti-NA antibodies protect from lethal influenza virus challenge in the mouse model and correlate inversely with virus shedding and symptoms in humans. Consequently, the NA is a promising target for influenza virus vaccine design. Current seasonal vaccines, however, poorly induce anti-NA antibodies, partly because of the immunodominance of the HA over the NA when the two glycoproteins are closely associated. To address this issue, here we investigated whether extending the stalk domain of the NA could render it more immunogenic on virus particles. Two recombinant influenza viruses based on the H1N1 strain A/Puerto Rico/8/1934 (PR8) were rescued with NA stalk domains extended by 15 or 30 amino acids. Formalin-inactivated viruses expressing wild-type NA or the stalk-extended NA variants were used to vaccinate mice. The virus with the 30-amino-acid stalk extension induced significantly higher anti-NA IgG responses (characterized by increased in vitro antibody-dependent cellular cytotoxicity [ADCC] activity) than the wild-type PR8 virus, while anti-HA IgG levels were unaffected. Similarly, extending the stalk domain of the NA of ...Continue Reading

References

Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·E D KilbourneB Grajower
Oct 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·B E JohanssonE D Kilbourne
Apr 1, 1974·The Journal of Infectious Diseases·R B CouchE D Kilbourne
Jun 22, 1972·The New England Journal of Medicine·B R MurphyR M Chanock
Feb 1, 1993·Journal of Virology·M R Castrucci, Y Kawaoka
Sep 1, 1996·Clinical and Diagnostic Laboratory Immunology·D C PowersB E Johansson
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Dec 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Audray HarrisAlasdair C Steven
Sep 12, 2007·Bioinformatics·M A LarkinD G Higgins
Dec 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Matthew R SandbulteMaryna C Eichelberger
Mar 23, 2012·Reviews in Medical Virology·Glendie MarcelinRichard J Webby
Mar 13, 2014·Vaccine·Ishrat SultanaMaryna C Eichelberger
Feb 28, 2015·Nature Reviews. Drug Discovery·Florian Krammer, Peter Palese
Apr 11, 2015·The Journal of Infectious Diseases·Arnold S MontoSuzanne E Ohmit
Jan 6, 2016·The Journal of Clinical Investigation·David J DiLilloJeffrey V Ravetch
Sep 30, 2016·Journal of Visualized Experiments : JoVE·Jin GaoMaryna C Eichelberger
Mar 20, 2018·Journal of Visualized Experiments : JoVE·Mark J BaileyGene S Tan

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Citations

Mar 3, 2020·Frontiers in Microbiology·Olivia A Vogel, Balaji Manicassamy
Apr 24, 2020·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·Angela ChoiMichael Schotsaert
Mar 24, 2021·Expert Opinion on Therapeutic Targets·Simone I Richardson, Penny L Moore

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