Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge
Identifieur interne : 000383 ( Pmc/Curation ); précédent : 000382; suivant : 000384Incorporation 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.
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
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<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>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Virol J</journal-id>
<journal-title>Virology Journal</journal-title>
<issn pub-type="epub">1743-422X</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
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<article-id pub-id-type="publisher-id">1743-422X-6-42</article-id>
<article-id pub-id-type="doi">10.1186/1743-422X-6-42</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge</article-title>
</title-group>
<contrib-group><contrib id="A1" contrib-type="author"><name><surname>Herbert</surname>
<given-names>Andrew S</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>asherbert@vt.edu</email>
</contrib>
<contrib id="A2" contrib-type="author"><name><surname>Heffron</surname>
<given-names>Lynn</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>cheffron@vt.edu</email>
</contrib>
<contrib id="A3" contrib-type="author"><name><surname>Sundick</surname>
<given-names>Roy</given-names>
</name>
<xref ref-type="aff" rid="I2">2</xref>
<email>rsundick@med.wayne.edu</email>
</contrib>
<contrib id="A4" corresp="yes" contrib-type="author"><name><surname>Roberts</surname>
<given-names>Paul C</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>pcroberts@vt.edu</email>
</contrib>
</contrib-group>
<aff id="I1"><label>1</label>
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</aff>
<aff id="I2"><label>2</label>
Department of Immunology/Microbiology, Wayne State University School of Medicine, 7374 Scott Hall, 540 E. Canfield Ave., Detroit, MI 48201, USA</aff>
<pub-date pub-type="collection"><year>2009</year>
</pub-date>
<pub-date pub-type="epub"><day>24</day>
<month>4</month>
<year>2009</year>
</pub-date>
<volume>6</volume>
<fpage>42</fpage>
<lpage>42</lpage>
<ext-link ext-link-type="uri" xlink:href="http://www.virologyj.com/content/6/1/42"></ext-link>
<history><date date-type="received"><day>10</day>
<month>4</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>24</day>
<month>4</month>
<year>2009</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2009 Herbert et al; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2009</copyright-year>
<copyright-holder>Herbert et al; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0"></ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
<pmc-comment>
Herbert
S
Andrew
asherbert@vt.edu
Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge
2009 Virology Journal 6(1): 42-. (2009) 1743-422X(2009)6:1<42> urn:ISSN:1743-422X </pmc-comment>
</license>
</permissions>
<abstract><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>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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