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Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus

Identifieur interne : 004469 ( Main/Exploration ); précédent : 004468; suivant : 004470

Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus

Auteurs : Raymond H. See [Canada] ; Alexander N. Zakhartchouk [Canada] ; Martin Petric [Canada] ; David J. Lawrence [Canada] ; Catherine P. Y. Mok [Canada] ; Robert J. Hogan [États-Unis] ; Thomas Rowe [États-Unis] ; Lois A. Zitzow [États-Unis] ; Karuna P. Karunakaran [Canada] ; Mary M. Hilt [Canada] ; Frank L. Graham [Canada] ; Ludvik Prevec [Canada] ; James B. Mahony [Canada] ; Chetna Sharon [Canada] ; Thierry C. Auperin [Canada] ; James M. Rini [Canada] ; Aubrey J. Tingle [Canada] ; David W. Scheifele [Canada] ; Danuta M. Skowronski [Canada] ; David M. Patrick [Canada] ; Thomas G. Voss [États-Unis] ; Lorne A. Babiuk [Canada] ; Jack Gauldie [Canada] ; Rachel L. Roper [États-Unis] ; Robert C. Brunham [Canada] ; B. Brett Finlay [Canada]

Source :

RBID : Pascal:06-0150208

Descripteurs français

English descriptors

Abstract

Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by /?-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.


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<title xml:lang="en" level="a">Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus</title>
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<title level="j" type="main">Journal of general virology</title>
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<term>Administration, Intranasal</term>
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<term>Antibodies, Viral (immunology)</term>
<term>Antibody Specificity</term>
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<term>Drug Evaluation, Preclinical</term>
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<term>Membrane Glycoproteins (immunology)</term>
<term>Mice</term>
<term>Microbiology</term>
<term>Mouse</term>
<term>Neutralization Tests</term>
<term>Nucleocapsid Proteins (genetics)</term>
<term>SARS Virus (chemistry)</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (prevention & control)</term>
<term>Severe acute respiratory syndrome</term>
<term>Severe acute respiratory syndrome virus</term>
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<term>Vaccine</term>
<term>Vaccines, DNA (administration & dosage)</term>
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<term>Modèles animaux de maladie humaine</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines nucléocapside (génétique)</term>
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<term>Vaccins antiviraux (administration et posologie)</term>
<term>Vaccins à ADN (administration et posologie)</term>
<term>Vaccins à ADN (génétique)</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (immunologie)</term>
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<term>Vaccines, DNA</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Antibodies, Viral</term>
<term>Immunoglobulin A</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Membrane Glycoproteins</term>
<term>Nucleocapsid Proteins</term>
<term>Vaccines, DNA</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Antibodies, Viral</term>
<term>Immunoglobulin A</term>
<term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</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="chemistry" 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>Protéines nucléocapside</term>
<term>Vaccins à ADN</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Glycoprotéines membranaires</term>
<term>Immunoglobuline A</term>
<term>Protéines de l'enveloppe virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</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>
<term>Immunoglobuline A</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Administration, Intranasal</term>
<term>Animals</term>
<term>Antibody Specificity</term>
<term>Disease Models, Animal</term>
<term>Drug Evaluation, Preclinical</term>
<term>Female</term>
<term>Injections, Intramuscular</term>
<term>Injections, Subcutaneous</term>
<term>Mice</term>
<term>Neutralization Tests</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Vaccination</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Administration par voie nasale</term>
<term>Animaux</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Injections musculaires</term>
<term>Injections sous-cutanées</term>
<term>Modèles animaux de maladie humaine</term>
<term>Souris</term>
<term>Spécificité des anticorps</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Tests de neutralisation</term>
<term>Vaccination</term>
<term>Virus du SRAS</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Vaccin</term>
<term>Microbiologie</term>
<term>Virologie</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Vaccin</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by /?-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Canada</li>
<li>États-Unis</li>
</country>
<region>
<li>Alabama</li>
<li>Caroline du Nord</li>
<li>Ontario</li>
</region>
<settlement>
<li>Hamilton (Ontario)</li>
<li>Toronto</li>
</settlement>
<orgName>
<li>Université McMaster</li>
<li>Université de Toronto</li>
</orgName>
</list>
<tree>
<country name="Canada">
<noRegion>
<name sortKey="See, Raymond H" sort="See, Raymond H" uniqKey="See R" first="Raymond H." last="See">Raymond H. See</name>
</noRegion>
<name sortKey="Auperin, Thierry C" sort="Auperin, Thierry C" uniqKey="Auperin T" first="Thierry C." last="Auperin">Thierry C. Auperin</name>
<name sortKey="Babiuk, Lorne A" sort="Babiuk, Lorne A" uniqKey="Babiuk L" first="Lorne A." last="Babiuk">Lorne A. Babiuk</name>
<name sortKey="Brunham, Robert C" sort="Brunham, Robert C" uniqKey="Brunham R" first="Robert C." last="Brunham">Robert C. Brunham</name>
<name sortKey="Finlay, B Brett" sort="Finlay, B Brett" uniqKey="Finlay B" first="B. Brett" last="Finlay">B. Brett Finlay</name>
<name sortKey="Gauldie, Jack" sort="Gauldie, Jack" uniqKey="Gauldie J" first="Jack" last="Gauldie">Jack Gauldie</name>
<name sortKey="Graham, Frank L" sort="Graham, Frank L" uniqKey="Graham F" first="Frank L." last="Graham">Frank L. Graham</name>
<name sortKey="Hilt, Mary M" sort="Hilt, Mary M" uniqKey="Hilt M" first="Mary M." last="Hilt">Mary M. Hilt</name>
<name sortKey="Karunakaran, Karuna P" sort="Karunakaran, Karuna P" uniqKey="Karunakaran K" first="Karuna P." last="Karunakaran">Karuna P. Karunakaran</name>
<name sortKey="Lawrence, David J" sort="Lawrence, David J" uniqKey="Lawrence D" first="David J." last="Lawrence">David J. Lawrence</name>
<name sortKey="Mahony, James B" sort="Mahony, James B" uniqKey="Mahony J" first="James B." last="Mahony">James B. Mahony</name>
<name sortKey="Mok, Catherine P Y" sort="Mok, Catherine P Y" uniqKey="Mok C" first="Catherine P. Y." last="Mok">Catherine P. Y. Mok</name>
<name sortKey="Patrick, David M" sort="Patrick, David M" uniqKey="Patrick D" first="David M." last="Patrick">David M. Patrick</name>
<name sortKey="Petric, Martin" sort="Petric, Martin" uniqKey="Petric M" first="Martin" last="Petric">Martin Petric</name>
<name sortKey="Prevec, Ludvik" sort="Prevec, Ludvik" uniqKey="Prevec L" first="Ludvik" last="Prevec">Ludvik Prevec</name>
<name sortKey="Rini, James M" sort="Rini, James M" uniqKey="Rini J" first="James M." last="Rini">James M. Rini</name>
<name sortKey="Scheifele, David W" sort="Scheifele, David W" uniqKey="Scheifele D" first="David W." last="Scheifele">David W. Scheifele</name>
<name sortKey="Sharon, Chetna" sort="Sharon, Chetna" uniqKey="Sharon C" first="Chetna" last="Sharon">Chetna Sharon</name>
<name sortKey="Skowronski, Danuta M" sort="Skowronski, Danuta M" uniqKey="Skowronski D" first="Danuta M." last="Skowronski">Danuta M. Skowronski</name>
<name sortKey="Tingle, Aubrey J" sort="Tingle, Aubrey J" uniqKey="Tingle A" first="Aubrey J." last="Tingle">Aubrey J. Tingle</name>
<name sortKey="Zakhartchouk, Alexander N" sort="Zakhartchouk, Alexander N" uniqKey="Zakhartchouk A" first="Alexander N." last="Zakhartchouk">Alexander N. Zakhartchouk</name>
</country>
<country name="États-Unis">
<region name="Alabama">
<name sortKey="Hogan, Robert J" sort="Hogan, Robert J" uniqKey="Hogan R" first="Robert J." last="Hogan">Robert J. Hogan</name>
</region>
<name sortKey="Roper, Rachel L" sort="Roper, Rachel L" uniqKey="Roper R" first="Rachel L." last="Roper">Rachel L. Roper</name>
<name sortKey="Rowe, Thomas" sort="Rowe, Thomas" uniqKey="Rowe T" first="Thomas" last="Rowe">Thomas Rowe</name>
<name sortKey="Voss, Thomas G" sort="Voss, Thomas G" uniqKey="Voss T" first="Thomas G." last="Voss">Thomas G. Voss</name>
<name sortKey="Zitzow, Lois A" sort="Zitzow, Lois A" uniqKey="Zitzow L" first="Lois A." last="Zitzow">Lois A. Zitzow</name>
</country>
</tree>
</affiliations>
</record>

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