A Novel Vaccination Strategy Mediating the Induction of Lung-Resident Memory CD8 T Cells Confers Heterosubtypic Immunity against Future Pandemic Influenza Virus.
Identifieur interne : 000560 ( PubMed/Corpus ); précédent : 000559; suivant : 000561A 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 ; Young-Tae Lee ; Min-Chul Kim ; Andrew T. Gewirtz ; Sang-Moo KangSource :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2016.
English descriptors
- KwdEn :
- Animals, CD8-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (virology), Cross Reactions, Female, Humans, Immunodominant Epitopes (administration & dosage), Immunodominant Epitopes (chemistry), Immunologic Memory, Influenza Vaccines (immunology), Influenza, Human (epidemiology), Influenza, Human (immunology), Influenza, Human (prevention & control), Interferon-gamma (metabolism), Lung (immunology), Lymphocyte Activation, Mass Vaccination (methods), Mice, Mice, Inbred BALB C, Orthomyxoviridae (immunology), Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (prevention & control), Pandemics, Viral Matrix Proteins (administration & dosage), Viral Matrix Proteins (chemistry), Virion (chemistry).
- MESH :
- chemical , administration & dosage : Immunodominant Epitopes, Viral Matrix Proteins.
- chemical , chemistry : Immunodominant Epitopes, Viral Matrix Proteins.
- chemistry : Virion.
- epidemiology : Influenza, Human.
- immunology : CD8-Positive T-Lymphocytes, Influenza Vaccines, Influenza, Human, Lung, Orthomyxoviridae, Orthomyxoviridae Infections.
- chemical , metabolism : Interferon-gamma.
- methods : Mass Vaccination.
- prevention & control : Influenza, Human, Orthomyxoviridae Infections.
- virology : CD8-Positive T-Lymphocytes.
- Animals, Cross Reactions, Female, Humans, Immunologic Memory, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Pandemics.
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. In this study, 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 extracellular domain of M2 (M2e) epitopes on virus-like particles (M2e5x VLP) that induced heterosubtypic immunity by eliciting Abs 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 Abs. Hence, vaccination with M2e5x VLP may be developable as a new strategy to combat future pandemic outbreaks.
DOI: 10.4049/jimmunol.1501637
PubMed: 26864033
Links to Exploration step
pubmed:26864033Le document en format XML
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<front><div type="abstract" xml:lang="en">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. In this study, 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 extracellular domain of M2 (M2e) epitopes on virus-like particles (M2e5x VLP) that induced heterosubtypic immunity by eliciting Abs 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 Abs. Hence, vaccination with M2e5x VLP may be developable as a new strategy to combat future pandemic outbreaks. </div>
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