Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice.
Identifieur interne : 000217 ( PubMed/Corpus ); précédent : 000216; suivant : 000218Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice.
Auteurs : Jeff Alexander ; Pamuk Bilsel ; Marie-France Del Guercio ; Stephani Stewart ; Aleksandra Marinkovic-Petrovic ; Scott Southwood ; Claire Crimi ; Lo Vang ; Les Walker ; Glenn Ishioka ; Vivek Chitnis ; Alessandro Sette ; Erika Assarsson ; Drew Hannaman ; Jason Botten ; Mark J. NewmanSource :
- Vaccine [ 1873-2518 ] ; 2010.
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.
DOI: 10.1016/j.vaccine.2009.10.103
PubMed: 19895924
Links to Exploration step
pubmed:19895924Le document en format XML
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Newman</name></author></analytic><series><title level="j">Vaccine</title><idno type="eISSN">1873-2518</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><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><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="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="prevention & control" xml:lang="en"><term>Influenza, Human</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></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 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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">19895924</PMID><DateCompleted><Year>2010</Year><Month>02</Month><Day>03</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-2518</ISSN><JournalIssue CitedMedium="Internet"><Volume>28</Volume><Issue>3</Issue><PubDate><Year>2010</Year><Month>Jan</Month><Day>08</Day></PubDate></JournalIssue><Title>Vaccine</Title><ISOAbbreviation>Vaccine</ISOAbbreviation></Journal><ArticleTitle>Universal influenza DNA vaccine encoding conserved CD4+ T cell epitopes protects against lethal viral challenge in HLA-DR transgenic mice.</ArticleTitle><Pagination><MedlinePgn>664-72</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.vaccine.2009.10.103</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alexander</LastName><ForeName>Jeff</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Pharmexa-Epimmune, Inc., San Diego, CA 92121, USA. jalexander@paxvax.com</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bilsel</LastName><ForeName>Pamuk</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>del Guercio</LastName><ForeName>Marie-France</ForeName><Initials>MF</Initials></Author><Author ValidYN="Y"><LastName>Stewart</LastName><ForeName>Stephani</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Marinkovic-Petrovic</LastName><ForeName>Aleksandra</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Southwood</LastName><ForeName>Scott</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Crimi</LastName><ForeName>Claire</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Vang</LastName><ForeName>Lo</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Walker</LastName><ForeName>Les</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Ishioka</LastName><ForeName>Glenn</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Chitnis</LastName><ForeName>Vivek</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Sette</LastName><ForeName>Alessandro</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Assarsson</LastName><ForeName>Erika</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Hannaman</LastName><ForeName>Drew</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Botten</LastName><ForeName>Jason</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Newman</LastName><ForeName>Mark J</ForeName><Initials>MJ</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>N01 AI030039</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>N01 AI030039-009</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>N01 AI040023</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>N01 AI-30039</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>11</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Vaccine</MedlineTA><NlmUniqueID>8406899</NlmUniqueID><ISSNLinking>0264-410X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018984">Epitopes, T-Lymphocyte</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D006684">HLA-DR Antigens</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007252">Influenza Vaccines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010455">Peptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019444">Vaccines, DNA</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017124" MajorTopicYN="N">Conserved Sequence</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018984" MajorTopicYN="N">Epitopes, T-Lymphocyte</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" 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Human</DescriptorName><QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007963" MajorTopicYN="N">Leukocytes, Mononuclear</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010455" MajorTopicYN="N">Peptides</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019444" 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