A DNA Vaccine That Targets Hemagglutinin to Antigen-Presenting Cells Protects Mice against H7 Influenza.
Identifieur interne : 000369 ( PubMed/Corpus ); précédent : 000368; suivant : 000370A DNA Vaccine That Targets Hemagglutinin to Antigen-Presenting Cells Protects Mice against H7 Influenza.
Auteurs : Tor Kristian Andersen ; Fan Zhou ; Rebecca Cox ; Bjarne Bogen ; Gunnveig Gr DelandSource :
- Journal of virology [ 1098-5514 ] ; 2017.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (blood), Antibodies, Viral (blood), Antigen-Presenting Cells (immunology), Hemagglutinin Glycoproteins, Influenza Virus (genetics), Hemagglutinin Glycoproteins, Influenza Virus (immunology), Histocompatibility Antigens Class II (genetics), Histocompatibility Antigens Class II (immunology), Humans, Influenza A Virus, H7N1 Subtype (genetics), Influenza A Virus, H7N1 Subtype (immunology), Influenza A Virus, H7N1 Subtype (pathogenicity), Influenza Vaccines (immunology), Influenza, Human (immunology), Influenza, Human (prevention & control), Mice, Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (prevention & control), Pandemics (prevention & control), Receptors, Chemokine (genetics), Receptors, Chemokine (immunology), Vaccines, DNA (administration & dosage), Vaccines, DNA (genetics), Vaccines, DNA (immunology).
- MESH :
- chemical , administration & dosage : Vaccines, DNA.
- chemical , blood : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , genetics : Hemagglutinin Glycoproteins, Influenza Virus, Histocompatibility Antigens Class II, Receptors, Chemokine, Vaccines, DNA.
- genetics : Influenza A Virus, H7N1 Subtype.
- immunology : Antigen-Presenting Cells, Hemagglutinin Glycoproteins, Influenza Virus, Histocompatibility Antigens Class II, Influenza A Virus, H7N1 Subtype, Influenza Vaccines, Influenza, Human, Orthomyxoviridae Infections, Receptors, Chemokine, Vaccines, DNA.
- pathogenicity : Influenza A Virus, H7N1 Subtype.
- prevention & control : Influenza, Human, Orthomyxoviridae Infections, Pandemics.
- Animals, Humans, Mice.
Abstract
Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently, no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to either major histocompatibility complex class II molecules or chemokine receptors 1, 3, and 5 (CCR1/3/5) that are expressed on antigen-presenting cells (APC). A single DNA vaccination with APC-targeted HA significantly increased antibody levels in sera compared to nontargeted control vaccines. The antibodies were confirmed neutralizing in an H7 pseudotype-based neutralization assay. Furthermore, the APC-targeted vaccines increased the levels of antigen-specific cytotoxic T cells, and a single DNA vaccination could confer protection against a lethal challenge with influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have developed a vaccine that rapidly could contribute protection against a pandemic threat from avian influenza.IMPORTANCE Highly pathogenic avian influenza H7 constitute a pandemic threat that can cause severe illness and death in infected individuals. Vaccination is the main method of prophylaxis against influenza, but current vaccine strategies fall short in a pandemic situation due to a prolonged production time and insufficient production capabilities. In contrast, a DNA vaccine can be rapidly produced and deployed to prevent the potential escalation of a highly pathogenic influenza pandemic. We here demonstrate that a single DNA delivery of hemagglutinin from an H7 influenza could mediate full protection against a lethal challenge with H7N1 influenza in mice. Vaccine efficacy was contingent on targeting of the secreted vaccine protein to antigen-presenting cells.
DOI: 10.1128/JVI.01340-17
PubMed: 28931687
Links to Exploration step
pubmed:28931687Le document en format XML
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Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Bogen, Bjarne" sort="Bogen, Bjarne" uniqKey="Bogen B" first="Bjarne" last="Bogen">Bjarne Bogen</name><affiliation><nlm:affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Gr Deland, Gunnveig" sort="Gr Deland, Gunnveig" uniqKey="Gr Deland G" first="Gunnveig" last="Gr Deland">Gunnveig Gr Deland</name><affiliation><nlm:affiliation>K. G. 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Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Zhou, Fan" sort="Zhou, Fan" uniqKey="Zhou F" first="Fan" last="Zhou">Fan Zhou</name><affiliation><nlm:affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Cox, Rebecca" sort="Cox, Rebecca" uniqKey="Cox R" first="Rebecca" last="Cox">Rebecca Cox</name><affiliation><nlm:affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Bogen, Bjarne" sort="Bogen, Bjarne" uniqKey="Bogen B" first="Bjarne" last="Bogen">Bjarne Bogen</name><affiliation><nlm:affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Gr Deland, Gunnveig" sort="Gr Deland, Gunnveig" uniqKey="Gr Deland G" first="Gunnveig" last="Gr Deland">Gunnveig Gr Deland</name><affiliation><nlm:affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway gunnveig.grodeland@medisin.uio.no.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Neutralizing (blood)</term><term>Antibodies, Viral (blood)</term><term>Antigen-Presenting Cells (immunology)</term><term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term><term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term><term>Histocompatibility Antigens Class II (genetics)</term><term>Histocompatibility Antigens Class II (immunology)</term><term>Humans</term><term>Influenza A Virus, H7N1 Subtype (genetics)</term><term>Influenza A Virus, H7N1 Subtype (immunology)</term><term>Influenza A Virus, H7N1 Subtype (pathogenicity)</term><term>Influenza Vaccines (immunology)</term><term>Influenza, Human (immunology)</term><term>Influenza, Human (prevention & control)</term><term>Mice</term><term>Orthomyxoviridae Infections (immunology)</term><term>Orthomyxoviridae Infections (prevention & control)</term><term>Pandemics (prevention & control)</term><term>Receptors, Chemokine (genetics)</term><term>Receptors, Chemokine (immunology)</term><term>Vaccines, DNA (administration & dosage)</term><term>Vaccines, DNA (genetics)</term><term>Vaccines, DNA (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Vaccines, DNA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hemagglutinin Glycoproteins, Influenza Virus</term><term>Histocompatibility Antigens Class II</term><term>Receptors, Chemokine</term><term>Vaccines, DNA</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H7N1 Subtype</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Antigen-Presenting Cells</term><term>Hemagglutinin Glycoproteins, Influenza Virus</term><term>Histocompatibility Antigens Class II</term><term>Influenza A Virus, H7N1 Subtype</term><term>Influenza Vaccines</term><term>Influenza, Human</term><term>Orthomyxoviridae Infections</term><term>Receptors, Chemokine</term><term>Vaccines, DNA</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Influenza A Virus, H7N1 Subtype</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Influenza, Human</term><term>Orthomyxoviridae Infections</term><term>Pandemics</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Mice</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently, no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to either major histocompatibility complex class II molecules or chemokine receptors 1, 3, and 5 (CCR1/3/5) that are expressed on antigen-presenting cells (APC). A single DNA vaccination with APC-targeted HA significantly increased antibody levels in sera compared to nontargeted control vaccines. The antibodies were confirmed neutralizing in an H7 pseudotype-based neutralization assay. Furthermore, the APC-targeted vaccines increased the levels of antigen-specific cytotoxic T cells, and a single DNA vaccination could confer protection against a lethal challenge with influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have developed a vaccine that rapidly could contribute protection against a pandemic threat from avian influenza.<b>IMPORTANCE</b> Highly pathogenic avian influenza H7 constitute a pandemic threat that can cause severe illness and death in infected individuals. Vaccination is the main method of prophylaxis against influenza, but current vaccine strategies fall short in a pandemic situation due to a prolonged production time and insufficient production capabilities. In contrast, a DNA vaccine can be rapidly produced and deployed to prevent the potential escalation of a highly pathogenic influenza pandemic. We here demonstrate that a single DNA delivery of hemagglutinin from an H7 influenza could mediate full protection against a lethal challenge with H7N1 influenza in mice. Vaccine efficacy was contingent on targeting of the secreted vaccine protein to antigen-presenting cells.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28931687</PMID><DateCompleted><Year>2017</Year><Month>12</Month><Day>06</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN><JournalIssue CitedMedium="Internet"><Volume>91</Volume><Issue>23</Issue><PubDate><Year>2017</Year><Month>12</Month><Day>01</Day></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>A DNA Vaccine That Targets Hemagglutinin to Antigen-Presenting Cells Protects Mice against H7 Influenza.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e01340-17</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.01340-17</ELocationID><Abstract><AbstractText>Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently, no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to either major histocompatibility complex class II molecules or chemokine receptors 1, 3, and 5 (CCR1/3/5) that are expressed on antigen-presenting cells (APC). A single DNA vaccination with APC-targeted HA significantly increased antibody levels in sera compared to nontargeted control vaccines. The antibodies were confirmed neutralizing in an H7 pseudotype-based neutralization assay. Furthermore, the APC-targeted vaccines increased the levels of antigen-specific cytotoxic T cells, and a single DNA vaccination could confer protection against a lethal challenge with influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have developed a vaccine that rapidly could contribute protection against a pandemic threat from avian influenza.<b>IMPORTANCE</b> Highly pathogenic avian influenza H7 constitute a pandemic threat that can cause severe illness and death in infected individuals. Vaccination is the main method of prophylaxis against influenza, but current vaccine strategies fall short in a pandemic situation due to a prolonged production time and insufficient production capabilities. In contrast, a DNA vaccine can be rapidly produced and deployed to prevent the potential escalation of a highly pathogenic influenza pandemic. We here demonstrate that a single DNA delivery of hemagglutinin from an H7 influenza could mediate full protection against a lethal challenge with H7N1 influenza in mice. Vaccine efficacy was contingent on targeting of the secreted vaccine protein to antigen-presenting cells.</AbstractText><CopyrightInformation>Copyright © 2017 Andersen et al.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Andersen</LastName><ForeName>Tor Kristian</ForeName><Initials>TK</Initials><AffiliationInfo><Affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Fan</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cox</LastName><ForeName>Rebecca</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Research and Development, Haukeland University Hospital, Bergen, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bogen</LastName><ForeName>Bjarne</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Immune Regulation, University of Oslo, Oslo, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grødeland</LastName><ForeName>Gunnveig</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>K. G. Jebsen Centre for Influenza Vaccine Research, University of Oslo and Oslo University Hospital, Oslo, Norway gunnveig.grodeland@medisin.uio.no.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>11</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Virol</MedlineTA><NlmUniqueID>0113724</NlmUniqueID><ISSNLinking>0022-538X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D057134">Antibodies, Neutralizing</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000914">Antibodies, 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