Immunization with Reverse-Genetics–Produced H5N1 Influenza Vaccine Protects Ferrets against Homologous and Heterologous Challenge
Identifieur interne : 001517 ( Main/Exploration ); précédent : 001516; suivant : 001518Immunization with Reverse-Genetics–Produced H5N1 Influenza Vaccine Protects Ferrets against Homologous and Heterologous Challenge
Auteurs : Elena A. Govorkova ; Richard J. Webby ; Jennifer Humberd ; Jon P. Seiler ; Robert G. WebsterSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2006.
Abstract
BackgroundMultiple cases of transmission of avian H5N1 influenza viruses to humans illustrate the urgent need for an efficacious, cross-protective vaccine MethodsFerrets were immunized with inactivated whole-virus vaccine produced by reverse genetics with the hemagglutinin (HA) and neuraminidase genes of A/HK/213/03 virus. Ferrets received a single dose of vaccine (7 or 15 μg of HA) with aluminum hydroxide adjuvant or 2 doses (7 μg of HA each) without adjuvant and were challenged with 106 50% egg infectious doses of A/HK/213/03, A/HK/156/97, or A/Vietnam/1203/04 virus ResultsOne or 2 doses of vaccine induced a protective antibody response to the vaccine strain. All immunization regimens completely protected ferrets from challenge with homologous wild-type A/HK/213/03 virus: no clinical signs of infection were observed, virus replication was significantly reduced (P<.05) and was restricted to the upper respiratory tract, and spread of virus to the brain was prevented. Importantly, all vaccinated ferrets were protected against lethal challenge with the highly pathogenic strain A/Vietnam/1203/04. The 2-dose schedule induced higher levels of antibodies that were cross-reactive to antigenically distinct H5N1 viruses ConclusionsH5N1 vaccines may stimulate an immune response that is more cross-protective than what might be predicted by in vitro assays and, thus, hold potential for being stockpiled as “initial” pandemic vaccines
Url:
DOI: 10.1086/505225
Affiliations:
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Webster</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField">Memphis</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date when="2006-07-15">2006</date><biblScope unit="vol">194</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="159">159</biblScope><biblScope unit="page" to="167">167</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">BackgroundMultiple cases of transmission of avian H5N1 influenza viruses to humans illustrate the urgent need for an efficacious, cross-protective vaccine MethodsFerrets were immunized with inactivated whole-virus vaccine produced by reverse genetics with the hemagglutinin (HA) and neuraminidase genes of A/HK/213/03 virus. Ferrets received a single dose of vaccine (7 or 15 μg of HA) with aluminum hydroxide adjuvant or 2 doses (7 μg of HA each) without adjuvant and were challenged with 106 50% egg infectious doses of A/HK/213/03, A/HK/156/97, or A/Vietnam/1203/04 virus ResultsOne or 2 doses of vaccine induced a protective antibody response to the vaccine strain. All immunization regimens completely protected ferrets from challenge with homologous wild-type A/HK/213/03 virus: no clinical signs of infection were observed, virus replication was significantly reduced (P<.05) and was restricted to the upper respiratory tract, and spread of virus to the brain was prevented. Importantly, all vaccinated ferrets were protected against lethal challenge with the highly pathogenic strain A/Vietnam/1203/04. The 2-dose schedule induced higher levels of antibodies that were cross-reactive to antigenically distinct H5N1 viruses ConclusionsH5N1 vaccines may stimulate an immune response that is more cross-protective than what might be predicted by in vitro assays and, thus, hold potential for being stockpiled as “initial” pandemic vaccines</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Govorkova, Elena A" sort="Govorkova, Elena A" uniqKey="Govorkova E" first="Elena A." last="Govorkova">Elena A. Govorkova</name><name sortKey="Humberd, Jennifer" sort="Humberd, Jennifer" uniqKey="Humberd J" first="Jennifer" last="Humberd">Jennifer Humberd</name><name sortKey="Seiler, Jon P" sort="Seiler, Jon P" uniqKey="Seiler J" first="Jon P." last="Seiler">Jon P. Seiler</name><name sortKey="Webby, Richard J" sort="Webby, Richard J" uniqKey="Webby R" first="Richard J." last="Webby">Richard J. 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