Heterosubtypic Protection Induced by a Live Attenuated Influenza Virus Vaccine Expressing Galactose-α-1,3-Galactose Epitopes in Infected Cells.

MBio
Li-Meng YanLeo L M Poon

Abstract

Anti-galactose-α-1,3-galactose (anti-α-Gal) antibody is naturally expressed at a high level in humans. It constitutes about 1% of immunoglobulins found in human blood. Here, we designed a live attenuated influenza virus vaccine that can generate α-Gal epitopes in infected cells in order to facilitate opsonization of infected cells, thereby enhancing vaccine-induced immune responses. In the presence of normal human sera, cells infected with this mutant can enhance phagocytosis of human macrophages and cytotoxicity of NK cells in vitro Using a knockout mouse strain that allows expression of anti-α-Gal antibody in vivo, we showed that this strategy can increase vaccine immunogenicity and the breadth of protection. This vaccine can induce 100% protection against a lethal heterosubtypic group 1 (H5) or group 2 (mouse-adapted H3) influenza virus challenge in the mouse model. In contrast, its heterosubtypic protective effect in wild-type or knockout mice that do not have anti-α-Gal antibody expression is only partial, demonstrating that the enhanced vaccine-induced protection requires anti-α-Gal antibody upon vaccination. Anti-α-Gal-expressing knockout mice immunized with this vaccine produce robust humoral and cell-mediated responses...Continue Reading

References

May 10, 2000·Proceedings of the National Academy of Sciences of the United States of America·E HoffmannR G Webster
Jul 2, 2008·The Journal of Experimental Medicine·Corine H GeurtsvanKesselBart N Lambrecht
Nov 17, 2009·Nature Immunology·William R Heath, Francis R Carbone
Aug 3, 2011·Journal of Leukocyte Biology·Tracy Voss CondonDavid W H Riches
Aug 24, 2011·The Journal of Experimental Medicine·A Nicole DeschClaudia V Jakubzick
Sep 13, 2011·American Journal of Respiratory Cell and Molecular Biology·Kazuki FuruhashiKingo Chida
Sep 13, 2012·Immunologic Research·A Nicole DeschClaudia V Jakubzick
Oct 9, 2012·The Journal of Clinical Investigation·Julie HelftMiriam Merad
Jan 16, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sinthujan JegaskandaStephen J Kent
May 16, 2013·American Journal of Respiratory Cell and Molecular Biology·Alexander V MisharinHarris Perlman
Jan 22, 2014·Nature Reviews. Immunology·Martin GuilliamsBart N Lambrecht
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Sophie A ValkenburgLeo L M Poon
Aug 14, 2015·Journal of Virology·Rebecca L Y FanLeo L M Poon
Apr 9, 2017·The Journal of Experimental Medicine·Christian H K LehmannDiana Dudziak
Dec 1, 2017·The New England Journal of Medicine·Catharine I PaulesAnthony S Fauci
Feb 23, 2018·Frontiers in Microbiology·Daniela S Rajão, Daniel R Pérez
Jun 12, 2018·Vaccine·Sophie A ValkenburgLeo L M Poon
Jun 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Hiroshi UekiYoshihiro Kawaoka
Jun 30, 2018·Nature Reviews. Disease Primers·Florian KrammerAdolfo García-Sastre
Nov 23, 2018·Nature Reviews. Immunology·S C Eisenbarth
Apr 6, 2019·Frontiers in Immunology·Carolyn M Boudreau, Galit Alter

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Citations

Aug 9, 2020·Frontiers in Immunology·Jessica L ChandrasekharLoren D Erickson
Sep 20, 2020·Trends in Parasitology·Adnan HodžićAlejandro Cabezas-Cruz

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Methods Mentioned

BETA
fluorescence-activated cell sorting
FACS
ELISA
reverse transcription-PCR
electrophoresis
enzyme-linked immunosorbent assay

Software Mentioned

GraphPad Prism
FlowJo

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