Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge
Identifieur interne : 003D65 ( Main/Exploration ); précédent : 003D64; suivant : 003D66Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge
Auteurs : Andrew S. Herbert [États-Unis] ; Lynn Heffron [États-Unis] ; Roy Sundick [États-Unis] ; Paul C. Roberts [États-Unis]Source :
- Virology Journal [ 1743-422X ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (sang), Charge virale, Chiens, Cytokines (génétique), Cytokines (immunologie), Facteurs immunologiques (génétique), Facteurs immunologiques (immunologie), Femelle, Infections à Orthomyxoviridae (), Infections à Orthomyxoviridae (immunologie), Infections à Orthomyxoviridae (virologie), Lignée cellulaire, Lymphocytes auxiliaires Th1 (immunologie), Poumon (virologie), Production d'anticorps (immunologie), Souris, Sous-type H1N1 du virus de la grippe A (génétique), Sous-type H1N1 du virus de la grippe A (immunologie), Sous-type H3N2 du virus de la grippe A (génétique), Sous-type H3N2 du virus de la grippe A (immunologie), Vaccins antigrippaux (immunologie), Vaccins inactivés (immunologie).
- MESH :
- génétique : Cytokines, Facteurs immunologiques, Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A.
- immunologie : Cytokines, Facteurs immunologiques, Infections à Orthomyxoviridae, Lymphocytes auxiliaires Th1, Production d'anticorps, Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Vaccins antigrippaux, Vaccins inactivés.
- sang : Anticorps antiviraux.
- virologie : Infections à Orthomyxoviridae, Poumon.
- Animaux, Charge virale, Chiens, Femelle, Infections à Orthomyxoviridae, Lignée cellulaire, Souris.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (blood), Antibody Formation (immunology), Cell Line, Cytokines (genetics), Cytokines (immunology), Dogs, Female, Immunologic Factors (genetics), Immunologic Factors (immunology), Influenza A Virus, H1N1 Subtype (genetics), Influenza A Virus, H1N1 Subtype (immunology), Influenza A Virus, H3N2 Subtype (genetics), Influenza A Virus, H3N2 Subtype (immunology), Influenza Vaccines (immunology), Lung (virology), Mice, Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (prevention & control), Orthomyxoviridae Infections (virology), Th1 Cells (immunology), Vaccines, Inactivated (immunology), Viral Load.
- MESH :
- chemical , blood : Antibodies, Viral.
- chemical , genetics : Cytokines, Immunologic Factors.
- genetics : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype.
- immunology : Antibody Formation, Cytokines, Immunologic Factors, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza Vaccines, Orthomyxoviridae Infections, Th1 Cells, Vaccines, Inactivated.
- prevention & control : Orthomyxoviridae Infections.
- virology : Lung, Orthomyxoviridae Infections.
- Animals, Cell Line, Dogs, Female, Mice, Viral Load.
Abstract
Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine.
We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4) fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release.
We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.
Url:
DOI: 10.1186/1743-422X-6-42
PubMed: 19393093
PubMed Central: 2679740
Affiliations:
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Le document en format XML
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Herbert</name><affiliation wicri:level="2"><nlm:aff id="I1">Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, 1981 Kraft Drive, Blacksburg, VA 24060, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, 1981 Kraft Drive, Blacksburg, VA 24060</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Heffron, Lynn" sort="Heffron, Lynn" uniqKey="Heffron L" first="Lynn" last="Heffron">Lynn Heffron</name><affiliation wicri:level="2"><nlm:aff id="I1">Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, 1981 Kraft Drive, Blacksburg, VA 24060, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, 1981 Kraft Drive, Blacksburg, VA 24060</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author><author><name sortKey="Sundick, Roy" sort="Sundick, Roy" uniqKey="Sundick R" first="Roy" last="Sundick">Roy Sundick</name><affiliation wicri:level="2"><nlm:aff id="I2">Department of Immunology/Microbiology, Wayne State University School of Medicine, 7374 Scott Hall, 540 E. Canfield Ave., Detroit, MI 48201, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunology/Microbiology, Wayne State University School of Medicine, 7374 Scott Hall, 540 E. Canfield Ave., Detroit, MI 48201</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Roberts, Paul C" sort="Roberts, Paul C" uniqKey="Roberts P" first="Paul C" last="Roberts">Paul C. 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(blood)</term><term>Antibody Formation (immunology)</term><term>Cell Line</term><term>Cytokines (genetics)</term><term>Cytokines (immunology)</term><term>Dogs</term><term>Female</term><term>Immunologic Factors (genetics)</term><term>Immunologic Factors (immunology)</term><term>Influenza A Virus, H1N1 Subtype (genetics)</term><term>Influenza A Virus, H1N1 Subtype (immunology)</term><term>Influenza A Virus, H3N2 Subtype (genetics)</term><term>Influenza A Virus, H3N2 Subtype (immunology)</term><term>Influenza Vaccines (immunology)</term><term>Lung (virology)</term><term>Mice</term><term>Orthomyxoviridae Infections (immunology)</term><term>Orthomyxoviridae Infections (prevention & control)</term><term>Orthomyxoviridae Infections (virology)</term><term>Th1 Cells (immunology)</term><term>Vaccines, Inactivated (immunology)</term><term>Viral Load</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (sang)</term><term>Charge virale</term><term>Chiens</term><term>Cytokines (génétique)</term><term>Cytokines (immunologie)</term><term>Facteurs immunologiques (génétique)</term><term>Facteurs immunologiques (immunologie)</term><term>Femelle</term><term>Infections à Orthomyxoviridae ()</term><term>Infections à Orthomyxoviridae (immunologie)</term><term>Infections à Orthomyxoviridae (virologie)</term><term>Lignée cellulaire</term><term>Lymphocytes auxiliaires Th1 (immunologie)</term><term>Poumon (virologie)</term><term>Production d'anticorps (immunologie)</term><term>Souris</term><term>Sous-type H1N1 du virus de la grippe A (génétique)</term><term>Sous-type H1N1 du virus de la grippe A (immunologie)</term><term>Sous-type H3N2 du virus de la grippe A (génétique)</term><term>Sous-type H3N2 du virus de la grippe A (immunologie)</term><term>Vaccins antigrippaux (immunologie)</term><term>Vaccins inactivés (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cytokines</term><term>Immunologic Factors</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Cytokines</term><term>Facteurs immunologiques</term><term>Sous-type H1N1 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cytokines</term><term>Facteurs immunologiques</term><term>Infections à Orthomyxoviridae</term><term>Lymphocytes auxiliaires Th1</term><term>Production d'anticorps</term><term>Sous-type H1N1 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Vaccins antigrippaux</term><term>Vaccins inactivés</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Antibody Formation</term><term>Cytokines</term><term>Immunologic Factors</term><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term><term>Influenza Vaccines</term><term>Orthomyxoviridae Infections</term><term>Th1 Cells</term><term>Vaccines, Inactivated</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à Orthomyxoviridae</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Dogs</term><term>Female</term><term>Mice</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Charge virale</term><term>Chiens</term><term>Femelle</term><term>Infections à Orthomyxoviridae</term><term>Lignée cellulaire</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine.</p></sec><sec><title>Results</title><p>We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4) fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. <italic>In vivo </italic>efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th<sub>1</sub>/Th<sub>2 </sub>humoral immune response, similar to live virus infections.</p></sec><sec><title>Conclusion</title><p>We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Michigan</li><li>Virginie</li></region></list><tree><country name="États-Unis"><region name="Virginie"><name sortKey="Herbert, Andrew S" sort="Herbert, Andrew S" uniqKey="Herbert A" first="Andrew S" last="Herbert">Andrew S. Herbert</name></region><name sortKey="Heffron, Lynn" sort="Heffron, Lynn" uniqKey="Heffron L" first="Lynn" last="Heffron">Lynn Heffron</name><name sortKey="Roberts, Paul C" sort="Roberts, Paul C" uniqKey="Roberts P" first="Paul C" last="Roberts">Paul C. Roberts</name><name sortKey="Sundick, Roy" sort="Sundick, Roy" uniqKey="Sundick R" first="Roy" last="Sundick">Roy Sundick</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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