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A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial

Identifieur interne : 001D58 ( Ncbi/Checkpoint ); précédent : 001D57; suivant : 001D59

A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial

Auteurs : Julie E. Martin [États-Unis] ; Mark K. Louder [États-Unis] ; Lasonji A. Holman [États-Unis] ; Ingelise J. Gordon [États-Unis] ; Mary E. Enama [États-Unis] ; Brenda D. Larkin [États-Unis] ; Charla A. Andrews [États-Unis] ; Leatrice Vogel [États-Unis] ; Richard A. Koup [États-Unis] ; Mario Roederer [États-Unis] ; Robert T. Bailer [États-Unis] ; Phillip L. Gomez [États-Unis] ; Martha Nason [États-Unis] ; John R. Mascola [États-Unis] ; Gary J. Nabel [États-Unis] ; Barney S. Graham [États-Unis]

Source :

RBID : PMC:2612543

Descripteurs français

English descriptors

Abstract

Background

The severe acute respiratory syndrome (SARS) virus is a member of the Coronaviridae (CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study.

Methods

A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization assays.

Results

The vaccine was well tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T-cell responses were detected in all vaccinees, and CD8+ T-cell responses in ∼20% of individuals.

Conclusions

The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults.


Url:
DOI: 10.1016/j.vaccine.2008.09.026
PubMed: 18824060
PubMed Central: 2612543


Affiliations:


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PMC:2612543

Le document en format XML

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<name sortKey="Roederer, Mario" sort="Roederer, Mario" uniqKey="Roederer M" first="Mario" last="Roederer">Mario Roederer</name>
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<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Nason, Martha" sort="Nason, Martha" uniqKey="Nason M" first="Martha" last="Nason">Martha Nason</name>
<affiliation wicri:level="2">
<nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, MSC-2610, Bethesda, MD 20892-3017, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Mascola, John R" sort="Mascola, John R" uniqKey="Mascola J" first="John R." last="Mascola">John R. Mascola</name>
<affiliation wicri:level="2">
<nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, MSC-2610, Bethesda, MD 20892-3017, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J." last="Nabel">Gary J. Nabel</name>
<affiliation wicri:level="2">
<nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, MSC-2610, Bethesda, MD 20892-3017, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, MSC-2610, Bethesda, MD 20892-3017</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S." last="Graham">Barney S. Graham</name>
<affiliation wicri:level="2">
<nlm:aff id="aff1">Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, MSC-2610, Bethesda, MD 20892-3017, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, MSC-2610, Bethesda, MD 20892-3017</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Vaccine</title>
<idno type="ISSN">0264-410X</idno>
<idno type="eISSN">1873-2518</idno>
<imprint>
<date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Adolescent</term>
<term>Adult</term>
<term>Antibodies, Viral (blood)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Middle Aged</term>
<term>Neutralization Tests</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (prevention & control)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Treatment Outcome</term>
<term>Vaccines, DNA (administration & dosage)</term>
<term>Vaccines, DNA (genetics)</term>
<term>Vaccines, DNA (immunology)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Vaccines (administration & dosage)</term>
<term>Viral Vaccines (genetics)</term>
<term>Viral Vaccines (immunology)</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Anticorps antiviraux (sang)</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Mâle</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Résultat thérapeutique</term>
<term>Syndrome respiratoire aigu sévère ()</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Tests de neutralisation</term>
<term>Vaccins antiviraux (administration et posologie)</term>
<term>Vaccins antiviraux (génétique)</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Vaccins à ADN (administration et posologie)</term>
<term>Vaccins à ADN (génétique)</term>
<term>Vaccins à ADN (immunologie)</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Vaccines, DNA</term>
<term>Viral Vaccines</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>Membrane Glycoproteins</term>
<term>Vaccines, DNA</term>
<term>Viral Envelope Proteins</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr">
<term>Vaccins antiviraux</term>
<term>Vaccins à ADN</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Vaccins antiviraux</term>
<term>Vaccins à ADN</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Glycoprotéines membranaires</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T CD8+</term>
<term>Protéines de l'enveloppe virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Vaccins antiviraux</term>
<term>Vaccins à ADN</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>CD4-Positive T-Lymphocytes</term>
<term>CD8-Positive T-Lymphocytes</term>
<term>Membrane Glycoproteins</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Vaccines, DNA</term>
<term>Viral Envelope Proteins</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en">
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr">
<term>Anticorps antiviraux</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adolescent</term>
<term>Adult</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Neutralization Tests</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Treatment Outcome</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Résultat thérapeutique</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Tests de neutralisation</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>The severe acute respiratory syndrome (SARS) virus is a member of the
<italic>Coronaviridae</italic>
(CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study.</p>
</sec>
<sec>
<title>Methods</title>
<p>A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization assays.</p>
</sec>
<sec>
<title>Results</title>
<p>The vaccine was well tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T-cell responses were detected in all vaccinees, and CD8+ T-cell responses in ∼20% of individuals.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults.</p>
</sec>
</div>
</front>
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<name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name>
</author>
<author>
<name sortKey="Manopo, I" uniqKey="Manopo I">I. Manopo</name>
</author>
<author>
<name sortKey="Leung, B P" uniqKey="Leung B">B.P. Leung</name>
</author>
<author>
<name sortKey="Chng, H H" uniqKey="Chng H">H.H. Chng</name>
</author>
<author>
<name sortKey="Ling, A E" uniqKey="Ling A">A.E. Ling</name>
</author>
<author>
<name sortKey="Chee, L L" uniqKey="Chee L">L.L. Chee</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name>
</author>
<author>
<name sortKey="Subbarao, K" uniqKey="Subbarao K">K. Subbarao</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Yang, L T" uniqKey="Yang L">L.T. Yang</name>
</author>
<author>
<name sortKey="Peng, H" uniqKey="Peng H">H. Peng</name>
</author>
<author>
<name sortKey="Zhu, Z L" uniqKey="Zhu Z">Z.L. Zhu</name>
</author>
<author>
<name sortKey="Li, G" uniqKey="Li G">G. Li</name>
</author>
<author>
<name sortKey="Huang, Z T" uniqKey="Huang Z">Z.T. Huang</name>
</author>
<author>
<name sortKey="Zhao, Z X" uniqKey="Zhao Z">Z.X. Zhao</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Peng, H" uniqKey="Peng H">H. Peng</name>
</author>
<author>
<name sortKey="Yang, L T" uniqKey="Yang L">L.T. Yang</name>
</author>
<author>
<name sortKey="Li, J" uniqKey="Li J">J. Li</name>
</author>
<author>
<name sortKey="Lu, Z Q" uniqKey="Lu Z">Z.Q. Lu</name>
</author>
<author>
<name sortKey="Wang, L Y" uniqKey="Wang L">L.Y. Wang</name>
</author>
<author>
<name sortKey="Koup, R A" uniqKey="Koup R">R.A. Koup</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Peng, H" uniqKey="Peng H">H. Peng</name>
</author>
<author>
<name sortKey="Yang, L T" uniqKey="Yang L">L.T. Yang</name>
</author>
<author>
<name sortKey="Wang, L Y" uniqKey="Wang L">L.Y. Wang</name>
</author>
<author>
<name sortKey="Li, J" uniqKey="Li J">J. Li</name>
</author>
<author>
<name sortKey="Huang, J" uniqKey="Huang J">J. Huang</name>
</author>
<author>
<name sortKey="Lu, Z Q" uniqKey="Lu Z">Z.Q. Lu</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Yang, L" uniqKey="Yang L">L. Yang</name>
</author>
<author>
<name sortKey="Peng, H" uniqKey="Peng H">H. Peng</name>
</author>
<author>
<name sortKey="Zhu, Z" uniqKey="Zhu Z">Z. Zhu</name>
</author>
<author>
<name sortKey="Li, G" uniqKey="Li G">G. Li</name>
</author>
<author>
<name sortKey="Huang, Z" uniqKey="Huang Z">Z. Huang</name>
</author>
<author>
<name sortKey="Zhao, Z" uniqKey="Zhao Z">Z. Zhao</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
<region>
<li>Maryland</li>
</region>
</list>
<tree>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Martin, Julie E" sort="Martin, Julie E" uniqKey="Martin J" first="Julie E." last="Martin">Julie E. Martin</name>
</region>
<name sortKey="Andrews, Charla A" sort="Andrews, Charla A" uniqKey="Andrews C" first="Charla A." last="Andrews">Charla A. Andrews</name>
<name sortKey="Bailer, Robert T" sort="Bailer, Robert T" uniqKey="Bailer R" first="Robert T." last="Bailer">Robert T. Bailer</name>
<name sortKey="Enama, Mary E" sort="Enama, Mary E" uniqKey="Enama M" first="Mary E." last="Enama">Mary E. Enama</name>
<name sortKey="Gomez, Phillip L" sort="Gomez, Phillip L" uniqKey="Gomez P" first="Phillip L." last="Gomez">Phillip L. Gomez</name>
<name sortKey="Gordon, Ingelise J" sort="Gordon, Ingelise J" uniqKey="Gordon I" first="Ingelise J." last="Gordon">Ingelise J. Gordon</name>
<name sortKey="Graham, Barney S" sort="Graham, Barney S" uniqKey="Graham B" first="Barney S." last="Graham">Barney S. Graham</name>
<name sortKey="Holman, Lasonji A" sort="Holman, Lasonji A" uniqKey="Holman L" first="Lasonji A." last="Holman">Lasonji A. Holman</name>
<name sortKey="Koup, Richard A" sort="Koup, Richard A" uniqKey="Koup R" first="Richard A." last="Koup">Richard A. Koup</name>
<name sortKey="Larkin, Brenda D" sort="Larkin, Brenda D" uniqKey="Larkin B" first="Brenda D." last="Larkin">Brenda D. Larkin</name>
<name sortKey="Louder, Mark K" sort="Louder, Mark K" uniqKey="Louder M" first="Mark K." last="Louder">Mark K. Louder</name>
<name sortKey="Mascola, John R" sort="Mascola, John R" uniqKey="Mascola J" first="John R." last="Mascola">John R. Mascola</name>
<name sortKey="Nabel, Gary J" sort="Nabel, Gary J" uniqKey="Nabel G" first="Gary J." last="Nabel">Gary J. Nabel</name>
<name sortKey="Nason, Martha" sort="Nason, Martha" uniqKey="Nason M" first="Martha" last="Nason">Martha Nason</name>
<name sortKey="Roederer, Mario" sort="Roederer, Mario" uniqKey="Roederer M" first="Mario" last="Roederer">Mario Roederer</name>
<name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name>
</country>
</tree>
</affiliations>
</record>

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