A novel vaccination strategy mediating the induction of lung-resident memory CD8 T cells confers heterosubtypic immunity against future pandemic influenza virus
Identifieur interne : 000464 ( Main/Exploration ); précédent : 000463; suivant : 000465A novel vaccination strategy mediating the induction of lung-resident memory CD8 T cells confers heterosubtypic immunity against future pandemic influenza virus
Auteurs : Yu-Na Lee [États-Unis] ; Young-Tae Lee [États-Unis] ; Min-Chul Kim [États-Unis, Corée du Sud] ; Andrew T. Gewirtz [États-Unis] ; Sang-Moo Kang [États-Unis]Source :
- Journal of immunology (Baltimore, Md. : 1950) [ 0022-1767 ] ; 2016.
Abstract
The currently used vaccine strategy to combat influenza A virus (IAV) aims to provide highly specific immunity to circulating seasonal IAV strains. However, the outbreak of 2009 influenza pandemic highlights the danger in this strategy. Here, we tested the hypothesis that universal vaccination that offers broader but weaker protection would result in cross protective T-cell responses after primary IAV infection, which would subsequently provide protective immunity against future pandemic strains. Specifically, we used tandem repeat M2e epitopes on virus-like particles (M2e5x VLP) that induced heterosubtypic immunity by eliciting antibodies to a conserved M2e epitope. M2e5x VLP was found to be superior to strain-specific current split vaccine in conferring heterosubtypic cross protection and in equipping the host with cross-protective lung-resident nucleoprotein-specific memory CD8+ T cell responses to a subsequent secondary infection with a new pandemic potential strain. Immune correlates for subsequent heterosubtypic immunity by M2e5x VLP vaccination were found to be virus-specific CD8+ T cells secreting IFN-γ and expressing lung-resident memory phenotypic markers CD69+ and CD103+ as well as M2e antibodies. Hence, vaccination with M2e5x VLP may be developable as a new strategy to combat future pandemic outbreaks.
Url:
DOI: 10.4049/jimmunol.1501637
PubMed: 26864033
PubMed Central: 4779729
Affiliations:
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However, the outbreak of 2009 influenza pandemic highlights the danger in this strategy. Here, we tested the hypothesis that universal vaccination that offers broader but weaker protection would result in cross protective T-cell responses after primary IAV infection, which would subsequently provide protective immunity against future pandemic strains. Specifically, we used tandem repeat M2e epitopes on virus-like particles (M2e5x VLP) that induced heterosubtypic immunity by eliciting antibodies to a conserved M2e epitope. M2e5x VLP was found to be superior to strain-specific current split vaccine in conferring heterosubtypic cross protection and in equipping the host with cross-protective lung-resident nucleoprotein-specific memory CD8<sup>+</sup> T cell responses to a subsequent secondary infection with a new pandemic potential strain. Immune correlates for subsequent heterosubtypic immunity by M2e5x VLP vaccination were found to be virus-specific CD8<sup>+</sup> T cells secreting IFN-γ and expressing lung-resident memory phenotypic markers CD69<sup>+</sup> and CD103<sup>+</sup> as well as M2e antibodies. Hence, vaccination with M2e5x VLP may be developable as a new strategy to combat future pandemic outbreaks.</p></div></front></TEI><affiliations><list><country><li>Corée du Sud</li><li>États-Unis</li></country><region><li>Géorgie (États-Unis)</li></region></list><tree><country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Lee, Yu Na" sort="Lee, Yu Na" uniqKey="Lee Y" first="Yu-Na" last="Lee">Yu-Na Lee</name></region><name sortKey="Gewirtz, Andrew T" sort="Gewirtz, Andrew T" uniqKey="Gewirtz A" first="Andrew T." last="Gewirtz">Andrew T. Gewirtz</name><name sortKey="Kang, Sang Moo" sort="Kang, Sang Moo" uniqKey="Kang S" first="Sang-Moo" last="Kang">Sang-Moo Kang</name><name sortKey="Kim, Min Chul" sort="Kim, Min Chul" uniqKey="Kim M" first="Min-Chul" last="Kim">Min-Chul Kim</name><name sortKey="Lee, Young Tae" sort="Lee, Young Tae" uniqKey="Lee Y" first="Young-Tae" last="Lee">Young-Tae Lee</name></country><country name="Corée du Sud"><noRegion><name sortKey="Kim, Min Chul" sort="Kim, Min Chul" uniqKey="Kim M" first="Min-Chul" last="Kim">Min-Chul Kim</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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