Immunization with Live Attenuated Influenza Viruses That Express Altered NS1 Proteins Results in Potent and Protective Memory CD8+ T-Cell Responses▿
Identifieur interne : 000A44 ( Pmc/Checkpoint ); précédent : 000A43; suivant : 000A45Immunization with Live Attenuated Influenza Viruses That Express Altered NS1 Proteins Results in Potent and Protective Memory CD8+ T-Cell Responses▿
Auteurs : Scott N. Mueller ; William A. Langley ; Elena Carnero ; Adolfo García-Sastre ; Rafi AhmedSource :
- Journal of Virology [ 0022-538X ] ; 2009.
Abstract
The generation of vaccines that induce long-lived protective immunity against influenza virus infections remains a challenging goal. Ideally, vaccines should elicit effective humoral and cellular immunity to protect an individual from infection or disease. Cross-reactive T- and B-cell responses that are elicited by live virus infections may provide such broad protection. Optimal induction of T-cell responses involves the action of type I interferons (IFN-I). Influenza virus expressed nonstructural protein 1 (NS1) functions as an inhibitor of IFN-I and promotes viral growth. We wanted to examine the priming of CD8+ T-cell responses to influenza virus in the absence of this inhibition of IFN-I production. We generated recombinant mouse-adapted influenza A/PR/8/34 viruses with NS1 truncations and/or deletions that also express the gp33-41 epitope from lymphocytic choriomeningitis virus. Intranasal infection of mice with the attenuated viruses primed long-lived T- and B-cell responses despite significantly reduced viral replication in the lungs compared to wild-type virus. Antigen-specific CD8+ T cells expanded upon rechallenge and generated increased protective memory T-cell populations after boosting. These results show that live attenuated influenza viruses expressing truncated NS1 proteins can prime protective immunity and may have implications for the design of novel modified live influenza virus vaccines.
Url:
DOI: 10.1128/JVI.01317-09
PubMed: 19939929
PubMed Central: 2812357
Affiliations:
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<front><div type="abstract" xml:lang="en"><p>The generation of vaccines that induce long-lived protective immunity against influenza virus infections remains a challenging goal. Ideally, vaccines should elicit effective humoral and cellular immunity to protect an individual from infection or disease. Cross-reactive T- and B-cell responses that are elicited by live virus infections may provide such broad protection. Optimal induction of T-cell responses involves the action of type I interferons (IFN-I). Influenza virus expressed nonstructural protein 1 (NS1) functions as an inhibitor of IFN-I and promotes viral growth. We wanted to examine the priming of CD8<sup>+</sup>
T-cell responses to influenza virus in the absence of this inhibition of IFN-I production. We generated recombinant mouse-adapted influenza A/PR/8/34 viruses with NS1 truncations and/or deletions that also express the gp33-41 epitope from lymphocytic choriomeningitis virus. Intranasal infection of mice with the attenuated viruses primed long-lived T- and B-cell responses despite significantly reduced viral replication in the lungs compared to wild-type virus. Antigen-specific CD8<sup>+</sup>
T cells expanded upon rechallenge and generated increased protective memory T-cell populations after boosting. These results show that live attenuated influenza viruses expressing truncated NS1 proteins can prime protective immunity and may have implications for the design of novel modified live influenza virus vaccines.</p>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="publisher-id">jvirol</journal-id>
<journal-title-group><journal-title>Journal of Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name>
</publisher>
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<article-meta><article-id pub-id-type="pmid">19939929</article-id>
<article-id pub-id-type="pmc">2812357</article-id>
<article-id pub-id-type="publisher-id">1317-09</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01317-09</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title>Immunization with Live Attenuated Influenza Viruses That Express Altered NS1 Proteins Results in Potent and Protective Memory CD8<sup>+</sup>
T-Cell Responses<xref ref-type="fn" rid="fn4">▿</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Mueller</surname>
<given-names>Scott N.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="fn" rid="fn1">†</xref>
<xref ref-type="fn" rid="fn2">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Langley</surname>
<given-names>William A.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="fn" rid="fn1">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Carnero</surname>
<given-names>Elena</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="fn" rid="fn3">§</xref>
</contrib>
<contrib contrib-type="author"><name><surname>García-Sastre</surname>
<given-names>Adolfo</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="aff" rid="aff1">3</xref>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ahmed</surname>
<given-names>Rafi</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
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<aff id="aff1">Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322,<label>1</label>
Department of Microbiology,<label>2</label>
Department of Medicine, Division of Infectious Diseases,<label>3</label>
Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York 10029<label>4</label>
</aff>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 727-3571. Fax: (404) 727-3722. E-mail: <email>rahmed@emory.edu</email>
</corresp>
<fn id="fn1"><label>†</label>
<p>S.N.M. and W.A.L. contributed equally to this study.</p>
</fn>
<fn id="fn2"><label>‡</label>
<p>Present address: Department of Microbiology and Immunology, The University of Melbourne, Parkville 3010, Australia.</p>
</fn>
<fn id="fn3"><label>§</label>
<p>Present address: Department of Gene Therapy and Hepatology, CIMA, University of Navarra, Pio XII, 55 Pamplona 31008, Spain.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>2</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub"><day>25</day>
<month>11</month>
<year>2009</year>
</pub-date>
<volume>84</volume>
<issue>4</issue>
<fpage>1847</fpage>
<lpage>1855</lpage>
<history><date date-type="received"><day>26</day>
<month>6</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>17</day>
<month>11</month>
<year>2009</year>
</date>
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<permissions><copyright-statement>Copyright © 2010, American Society for Microbiology</copyright-statement>
<copyright-year>2010</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:href="zjv00410001847.pdf"></self-uri>
<abstract><p>The generation of vaccines that induce long-lived protective immunity against influenza virus infections remains a challenging goal. Ideally, vaccines should elicit effective humoral and cellular immunity to protect an individual from infection or disease. Cross-reactive T- and B-cell responses that are elicited by live virus infections may provide such broad protection. Optimal induction of T-cell responses involves the action of type I interferons (IFN-I). Influenza virus expressed nonstructural protein 1 (NS1) functions as an inhibitor of IFN-I and promotes viral growth. We wanted to examine the priming of CD8<sup>+</sup>
T-cell responses to influenza virus in the absence of this inhibition of IFN-I production. We generated recombinant mouse-adapted influenza A/PR/8/34 viruses with NS1 truncations and/or deletions that also express the gp33-41 epitope from lymphocytic choriomeningitis virus. Intranasal infection of mice with the attenuated viruses primed long-lived T- and B-cell responses despite significantly reduced viral replication in the lungs compared to wild-type virus. Antigen-specific CD8<sup>+</sup>
T cells expanded upon rechallenge and generated increased protective memory T-cell populations after boosting. These results show that live attenuated influenza viruses expressing truncated NS1 proteins can prime protective immunity and may have implications for the design of novel modified live influenza virus vaccines.</p>
</abstract>
</article-meta>
</front>
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<tree><noCountry><name sortKey="Ahmed, Rafi" sort="Ahmed, Rafi" uniqKey="Ahmed R" first="Rafi" last="Ahmed">Rafi Ahmed</name>
<name sortKey="Carnero, Elena" sort="Carnero, Elena" uniqKey="Carnero E" first="Elena" last="Carnero">Elena Carnero</name>
<name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name>
<name sortKey="Langley, William A" sort="Langley, William A" uniqKey="Langley W" first="William A." last="Langley">William A. Langley</name>
<name sortKey="Mueller, Scott N" sort="Mueller, Scott N" uniqKey="Mueller S" first="Scott N." last="Mueller">Scott N. Mueller</name>
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