Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice
Identifieur interne : 000F86 ( Main/Exploration ); précédent : 000F85; suivant : 000F87Universal 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] ; Markj. Newman [États-Unis]Source :
- Vaccine [ 0264-410X ] ; 2010.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Animal transgénique.
English descriptors
- KwdEn :
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<TM> 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.
Affiliations:
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aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Stewart, Stephani" sort="Stewart, Stephani" uniqKey="Stewart S" first="Stephani" last="Stewart">Stephani Stewart</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Pharmexa-Epimmune, Inc.</s1><s2>San Diego, CA</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Marinkovic Petrovic, Aleksandra" sort="Marinkovic Petrovic, Aleksandra" uniqKey="Marinkovic Petrovic A" first="Aleksandra" last="Marinkovic-Petrovic">Aleksandra Marinkovic-Petrovic</name><affiliation wicri:level="2"><inist:fA14 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type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Walker, Les" sort="Walker, Les" uniqKey="Walker L" first="Les" last="Walker">Les Walker</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Pharmexa-Epimmune, Inc.</s1><s2>San Diego, CA</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Ishioka, Glenn" sort="Ishioka, Glenn" uniqKey="Ishioka G" first="Glenn" last="Ishioka">Glenn Ishioka</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Pharmexa-Epimmune, Inc.</s1><s2>San Diego, CA</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Chitnis, Vivek" sort="Chitnis, Vivek" uniqKey="Chitnis V" first="Vivek" last="Chitnis">Vivek Chitnis</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Pharmexa-Epimmune, Inc.</s1><s2>San Diego, CA</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Sette, Alessandro" sort="Sette, Alessandro" uniqKey="Sette A" first="Alessandro" last="Sette">Alessandro Sette</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>La Jolla Institute for Allergy and Immunology</s1><s2>San Diego, CA</s2><s3>USA</s3><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Assarsson, Erika" sort="Assarsson, Erika" uniqKey="Assarsson E" first="Erika" last="Assarsson">Erika Assarsson</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>La Jolla Institute for Allergy and Immunology</s1><s2>San Diego, CA</s2><s3>USA</s3><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Hannaman, Drew" sort="Hannaman, Drew" uniqKey="Hannaman D" first="Drew" last="Hannaman">Drew Hannaman</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Ichor Medical Systems, Inc.</s1><s2>San Diego, CA</s2><s3>USA</s3><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Botten, Jason" sort="Botten, Jason" uniqKey="Botten J" first="Jason" last="Botten">Jason Botten</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>The University of Vermont College of Medicine</s1><s2>Burlington, VT</s2><s3>USA</s3><sZ>15 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Vermont</region></placeName></affiliation></author><author><name sortKey="Newman, Markj" sort="Newman, Markj" uniqKey="Newman M" first="Markj." last="Newman">Markj. Newman</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Pharmexa-Epimmune, Inc.</s1><s2>San Diego, CA</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibody</term><term>Antigenic determinant</term><term>CD4 T lymphocyte</term><term>Genetic vaccine</term><term>HLA-System</term><term>Influenza</term><term>Mouse</term><term>Transgenic animal</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animal transgénique</term><term>Souris</term><term>Vaccin génétique</term><term>Lymphocyte T CD4</term><term>Déterminant antigénique</term><term>Système HLA</term><term>Anticorps</term><term>Grippe</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Animal transgénique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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<<sup>TM</sup>> 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<sup>+</sup> T cell responses to protection against influenza infection.</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, Markj" sort="Newman, Markj" uniqKey="Newman M" first="Markj." last="Newman">Markj. 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>Pour manipuler ce document sous Unix (Dilib)
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