A novel vaccination strategy mediating the induction of lung-resident memory CD8 T cells confers heterosubtypic immunity against future pandemic influenza virus
Identifieur interne : 000915 ( Main/Exploration ); précédent : 000914; suivant : 000916A 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.
Descripteurs français
- KwdFr :
- Activation des lymphocytes, Animaux, Femelle, Grippe humaine (), Grippe humaine (immunologie), Grippe humaine (épidémiologie), Humains, Infections à Orthomyxoviridae (), Infections à Orthomyxoviridae (immunologie), Interféron gamma (métabolisme), Lymphocytes T CD8+ (immunologie), Lymphocytes T CD8+ (virologie), Mémoire immunologique, Orthomyxoviridae (immunologie), Pandémies, Poumon (immunologie), Protéines de la matrice virale (), Protéines de la matrice virale (administration et posologie), Réactions croisées, Souris, Souris de lignée BALB C, Vaccination de masse (), Vaccins antigrippaux (immunologie), Virion (), Épitopes immunodominants (), Épitopes immunodominants (administration et posologie).
- MESH :
- administration et posologie : Protéines de la matrice virale, Épitopes immunodominants.
- immunologie : Grippe humaine, Infections à Orthomyxoviridae, Lymphocytes T CD8+, Orthomyxoviridae, Poumon, Vaccins antigrippaux.
- métabolisme : Interféron gamma.
- virologie : Lymphocytes T CD8+.
- épidémiologie : Grippe humaine.
- Activation des lymphocytes, Animaux, Femelle, Grippe humaine, Humains, Infections à Orthomyxoviridae, Mémoire immunologique, Pandémies, Protéines de la matrice virale, Réactions croisées, Souris, Souris de lignée BALB C, Vaccination de masse, Virion, Épitopes immunodominants.
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. 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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<term>CD8-Positive T-Lymphocytes (virology)</term>
<term>Cross Reactions</term>
<term>Female</term>
<term>Humans</term>
<term>Immunodominant Epitopes (administration & dosage)</term>
<term>Immunodominant Epitopes (chemistry)</term>
<term>Immunologic Memory</term>
<term>Influenza Vaccines (immunology)</term>
<term>Influenza, Human (epidemiology)</term>
<term>Influenza, Human (immunology)</term>
<term>Influenza, Human (prevention & control)</term>
<term>Interferon-gamma (metabolism)</term>
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<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Orthomyxoviridae (immunology)</term>
<term>Orthomyxoviridae Infections (immunology)</term>
<term>Orthomyxoviridae Infections (prevention & control)</term>
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<term>Grippe humaine (immunologie)</term>
<term>Grippe humaine (épidémiologie)</term>
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<term>Infections à Orthomyxoviridae ()</term>
<term>Infections à Orthomyxoviridae (immunologie)</term>
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<term>Épitopes immunodominants (administration et posologie)</term>
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<term>Cross Reactions</term>
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<term>Humans</term>
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<term>Grippe humaine</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae</term>
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<front><div type="abstract" xml:lang="en"><p id="P1">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<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>
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