H2N2V1, Main, Exploration, bibRecord, 001023

Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice

Identifieur interne : 001023 ( Main/Exploration ); précédent : 001022; suivant : 001024

Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice

Auteurs : Jeff Alexander [États-Unis] ; Pamuk Bilsel [États-Unis] ; Marie-France Del Guercio [États-Unis] ; Stephani Stewart [États-Unis] ; Aleksandra Marinkovic-Petrovic [États-Unis] ; Scott Southwood [États-Unis] ; Claire Crimi [États-Unis] ; Lo Vang [États-Unis] ; Les Walker [États-Unis] ; Glenn Ishioka [États-Unis] ; Vivek Chitnis [États-Unis] ; Alessandro Sette [États-Unis] ; Erika Assarsson [États-Unis] ; Drew Hannaman [États-Unis] ; Jason Botten [États-Unis] ; Mark J. Newman [États-Unis]

Source :

Vaccine [ 0264-410X ] ; 2009.

RBID : PMC:3364000

Descripteurs français

English descriptors

KwdEn :
- Animals, Antibodies, Viral (blood), Cells, Cultured, Conserved Sequence (genetics), Conserved Sequence (immunology), Epitopes, T-Lymphocyte (genetics), Epitopes, T-Lymphocyte (immunology), HLA-DR Antigens (immunology), HLA-DR Antigens (metabolism), Humans, Influenza A virus (genetics), Influenza A virus (immunology), Influenza Vaccines (genetics), Influenza Vaccines (immunology), Influenza, Human (prevention & control), Leukocytes, Mononuclear (immunology), Mice, Mice, Transgenic, Peptides (immunology), Peptides (metabolism), Protein Binding, Survival Analysis, Vaccines, DNA (genetics), Vaccines, DNA (immunology).
MESH :
- chemical , blood : Antibodies, Viral.
- genetics : Conserved Sequence, Epitopes, T-Lymphocyte, Influenza A virus, Influenza Vaccines, Vaccines, DNA.
- immunology : Conserved Sequence, Epitopes, T-Lymphocyte, HLA-DR Antigens, Influenza A virus, Influenza Vaccines, Leukocytes, Mononuclear, Peptides, Vaccines, DNA.
- chemical , metabolism : HLA-DR Antigens, Peptides.
- prevention & control : Influenza, Human.
- Animals, Cells, Cultured, Humans, Mice, Mice, Transgenic, Protein Binding, Survival Analysis.

Abstract

The goal of the present study was to design a vaccine that would provide universal protection against infection of humans with diverse influenza A viruses. Accordingly, protein sequences from influenza A virus strains currently in circulation (H1N1, H3N2), agents of past pandemics (H1N1, H2N2, H3N2) and zoonotic infections of man (H1N1, H5N1, H7N2, H7N3, H7N7, H9N2) were evaluated for the presence of amino acid sequences, motifs, that are predicted to mediate peptide epitope binding with high affinity to the most frequent HLA-DR allelic products. Peptides conserved among diverse influenza strains were then synthesized, evaluated for binding to purified HLA-DR molecules and for their capacity to induce influenza-specific immune recall responses using human donor peripheral blood mononuclear cells (PBMC). Accordingly, 20 epitopes were selected for further investigation based on their conservancy among diverse influenza strains, predicted population coverage in diverse ethnic groups and capacity to recall influenza-specific responses. A DNA plasmid encoding the epitopes was constructed using amino acid spacers between epitopes to promote optimum processing and presentation. Immunogenicity of the DNA vaccine was measured using HLA-DR4 transgenic mice and the TriGrid™ in vivo electroporation device. Vaccination resulted in peptide-specific immune responses, augmented HA-specific antibody responses and protection of HLA-DR4 transgenic mice from lethal PR8 influenza virus challenge. These studies demonstrate the utility of this vaccine format and the contribution of CD4⁺ T cell responses to protection against influenza infection.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364000

DOI: 10.1016/j.vaccine.2009.10.103
PubMed: 19895924
PubMed Central: 3364000

Affiliations:

Le document en format XML

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 T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice</title>
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<author><name sortKey="Ishioka, Glenn" sort="Ishioka, Glenn" uniqKey="Ishioka G" first="Glenn" last="Ishioka">Glenn Ishioka</name>
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 T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice</title>
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</placeName>
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<author><name sortKey="Southwood, Scott" sort="Southwood, Scott" uniqKey="Southwood S" first="Scott" last="Southwood">Scott Southwood</name>
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<author><name sortKey="Crimi, Claire" sort="Crimi, Claire" uniqKey="Crimi C" first="Claire" last="Crimi">Claire Crimi</name>
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<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Pharmexa-Epimmune Inc., San Diego</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Vang, Lo" sort="Vang, Lo" uniqKey="Vang L" first="Lo" last="Vang">Lo Vang</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Pharmexa-Epimmune Inc., San Diego, California</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Pharmexa-Epimmune Inc., San Diego</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Walker, Les" sort="Walker, Les" uniqKey="Walker L" first="Les" last="Walker">Les Walker</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Pharmexa-Epimmune Inc., San Diego, California</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Pharmexa-Epimmune Inc., San Diego</wicri:cityArea>
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</author>
<author><name sortKey="Ishioka, Glenn" sort="Ishioka, Glenn" uniqKey="Ishioka G" first="Glenn" last="Ishioka">Glenn Ishioka</name>
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<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Pharmexa-Epimmune Inc., San Diego</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Chitnis, Vivek" sort="Chitnis, Vivek" uniqKey="Chitnis V" first="Vivek" last="Chitnis">Vivek Chitnis</name>
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<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Pharmexa-Epimmune Inc., San Diego</wicri:cityArea>
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<author><name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name>
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<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>La Jolla Institute for Allergy and Immunology, San Diego</wicri:cityArea>
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<author><name sortKey="Assarsson, Erika" sort="Assarsson, Erika" uniqKey="Assarsson E" first="Erika" last="Assarsson">Erika Assarsson</name>
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</placeName>
<wicri:cityArea>La Jolla Institute for Allergy and Immunology, San Diego</wicri:cityArea>
</affiliation>
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<author><name sortKey="Hannaman, Drew" sort="Hannaman, Drew" uniqKey="Hannaman D" first="Drew" last="Hannaman">Drew Hannaman</name>
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</placeName>
<wicri:cityArea>Ichor Medical Systems, Inc., San Diego</wicri:cityArea>
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<author><name sortKey="Botten, Jason" sort="Botten, Jason" uniqKey="Botten J" first="Jason" last="Botten">Jason Botten</name>
<affiliation wicri:level="2"><nlm:aff id="A4">The University of Vermont College of Medicine, Burlington, Vermont</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Vermont</region>
</placeName>
<wicri:cityArea>The University of Vermont College of Medicine, Burlington</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Newman, Mark J" sort="Newman, Mark J" uniqKey="Newman M" first="Mark J" last="Newman">Mark J. Newman</name>
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<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
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</affiliation>
</author>
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<term>Antibodies, Viral (blood)</term>
<term>Cells, Cultured</term>
<term>Conserved Sequence (genetics)</term>
<term>Conserved Sequence (immunology)</term>
<term>Epitopes, T-Lymphocyte (genetics)</term>
<term>Epitopes, T-Lymphocyte (immunology)</term>
<term>HLA-DR Antigens (immunology)</term>
<term>HLA-DR Antigens (metabolism)</term>
<term>Humans</term>
<term>Influenza A virus (genetics)</term>
<term>Influenza A virus (immunology)</term>
<term>Influenza Vaccines (genetics)</term>
<term>Influenza Vaccines (immunology)</term>
<term>Influenza, Human (prevention & control)</term>
<term>Leukocytes, Mononuclear (immunology)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Peptides (immunology)</term>
<term>Peptides (metabolism)</term>
<term>Protein Binding</term>
<term>Survival Analysis</term>
<term>Vaccines, DNA (genetics)</term>
<term>Vaccines, DNA (immunology)</term>
</keywords>
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<term>Animaux</term>
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<term>Antigènes HLA-DR (immunologie)</term>
<term>Antigènes HLA-DR (métabolisme)</term>
<term>Cellules cultivées</term>
<term>Déterminants antigéniques des lymphocytes T (génétique)</term>
<term>Déterminants antigéniques des lymphocytes T (immunologie)</term>
<term>Grippe humaine ()</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Peptides (immunologie)</term>
<term>Peptides (métabolisme)</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Séquence conservée (génétique)</term>
<term>Séquence conservée (immunologie)</term>
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<term>Vaccins antigrippaux (immunologie)</term>
<term>Vaccins à ADN (génétique)</term>
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<term>Virus de la grippe A (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Conserved Sequence</term>
<term>Epitopes, T-Lymphocyte</term>
<term>Influenza A virus</term>
<term>Influenza Vaccines</term>
<term>Vaccines, DNA</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Déterminants antigéniques des lymphocytes T</term>
<term>Séquence conservée</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins à ADN</term>
<term>Virus de la grippe A</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Agranulocytes</term>
<term>Antigènes HLA-DR</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Peptides</term>
<term>Séquence conservée</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins à ADN</term>
<term>Virus de la grippe A</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Conserved Sequence</term>
<term>Epitopes, T-Lymphocyte</term>
<term>HLA-DR Antigens</term>
<term>Influenza A virus</term>
<term>Influenza Vaccines</term>
<term>Leukocytes, Mononuclear</term>
<term>Peptides</term>
<term>Vaccines, DNA</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>HLA-DR Antigens</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes HLA-DR</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Influenza, Human</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cells, Cultured</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Protein Binding</term>
<term>Survival Analysis</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term>
<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Grippe humaine</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Souris</term>
<term>Souris transgéniques</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P3">The goal of the present study was to design a vaccine that would provide universal protection against infection of humans with diverse influenza A viruses. Accordingly, protein sequences from influenza A virus strains currently in circulation (H1N1, H3N2), agents of past pandemics (H1N1, H2N2, H3N2) and zoonotic infections of man (H1N1, H5N1, H7N2, H7N3, H7N7, H9N2) were evaluated for the presence of amino acid sequences, motifs, that are predicted to mediate peptide epitope binding with high affinity to the most frequent HLA-DR allelic products. Peptides conserved among diverse influenza strains were then synthesized, evaluated for binding to purified HLA-DR molecules and for their capacity to induce influenza-specific immune recall responses using human donor peripheral blood mononuclear cells (PBMC). Accordingly, 20 epitopes were selected for further investigation based on their conservancy among diverse influenza strains, predicted population coverage in diverse ethnic groups and capacity to recall influenza-specific responses. A DNA plasmid encoding the epitopes was constructed using amino acid spacers between epitopes to promote optimum processing and presentation. Immunogenicity of the DNA vaccine was measured using HLA-DR4 transgenic mice and the TriGrid™ <italic>in vivo</italic>
 electroporation device. Vaccination resulted in peptide-specific immune responses, augmented HA-specific antibody responses and protection of HLA-DR4 transgenic mice from lethal PR8 influenza virus challenge. These studies demonstrate the utility of this vaccine format and the contribution of CD4<sup>+</sup>
 T cell responses to protection against influenza infection.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Vermont</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Californie"><name sortKey="Alexander, Jeff" sort="Alexander, Jeff" uniqKey="Alexander J" first="Jeff" last="Alexander">Jeff Alexander</name>
</region>
<name sortKey="Assarsson, Erika" sort="Assarsson, Erika" uniqKey="Assarsson E" first="Erika" last="Assarsson">Erika Assarsson</name>
<name sortKey="Bilsel, Pamuk" sort="Bilsel, Pamuk" uniqKey="Bilsel P" first="Pamuk" last="Bilsel">Pamuk Bilsel</name>
<name sortKey="Botten, Jason" sort="Botten, Jason" uniqKey="Botten J" first="Jason" last="Botten">Jason Botten</name>
<name sortKey="Chitnis, Vivek" sort="Chitnis, Vivek" uniqKey="Chitnis V" first="Vivek" last="Chitnis">Vivek Chitnis</name>
<name sortKey="Crimi, Claire" sort="Crimi, Claire" uniqKey="Crimi C" first="Claire" last="Crimi">Claire Crimi</name>
<name sortKey="Del Guercio, Marie France" sort="Del Guercio, Marie France" uniqKey="Del Guercio M" first="Marie-France" last="Del Guercio">Marie-France Del Guercio</name>
<name sortKey="Hannaman, Drew" sort="Hannaman, Drew" uniqKey="Hannaman D" first="Drew" last="Hannaman">Drew Hannaman</name>
<name sortKey="Ishioka, Glenn" sort="Ishioka, Glenn" uniqKey="Ishioka G" first="Glenn" last="Ishioka">Glenn Ishioka</name>
<name sortKey="Marinkovic Petrovic, Aleksandra" sort="Marinkovic Petrovic, Aleksandra" uniqKey="Marinkovic Petrovic A" first="Aleksandra" last="Marinkovic-Petrovic">Aleksandra Marinkovic-Petrovic</name>
<name sortKey="Newman, Mark J" sort="Newman, Mark J" uniqKey="Newman M" first="Mark J" last="Newman">Mark J. Newman</name>
<name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name>
<name sortKey="Southwood, Scott" sort="Southwood, Scott" uniqKey="Southwood S" first="Scott" last="Southwood">Scott Southwood</name>
<name sortKey="Stewart, Stephani" sort="Stewart, Stephani" uniqKey="Stewart S" first="Stephani" last="Stewart">Stephani Stewart</name>
<name sortKey="Vang, Lo" sort="Vang, Lo" uniqKey="Vang L" first="Lo" last="Vang">Lo Vang</name>
<name sortKey="Walker, Les" sort="Walker, Les" uniqKey="Walker L" first="Les" last="Walker">Les Walker</name>
</country>
</tree>
</affiliations>
</record>

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Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice

Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice

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