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Immunogenicity of a receptor-binding domain of SARS coronavirus spike protein in mice : Implications for a subunit vaccine

Identifieur interne : 003B63 ( Main/Exploration ); précédent : 003B62; suivant : 003B64

Immunogenicity of a receptor-binding domain of SARS coronavirus spike protein in mice : Implications for a subunit vaccine

Auteurs : Alexander N. Zakhartchouk [Canada] ; Chetna Sharon [Canada] ; Malathy Satkunarajah [Canada] ; Thierry Auperin [Canada] ; Sathiyanarayanan Viswanathan [Canada] ; George Mutwiri [Canada] ; Martin Petric [Canada] ; Raymond H. See [Canada] ; Robert C. Brunham [Canada] ; B. Brett Finlay [Canada] ; Cheryl Cameron [Canada] ; David J. Kelvin [Canada] ; Alan Cochrane [Canada] ; James M. Rini [Canada] ; Lorne A. Babiuk [Canada]

Source :

RBID : Pascal:07-0078280

Descripteurs français

English descriptors

Abstract

We studied the immunogenicity of an anti-SARS subunit vaccine comprised of the fragment of the SARS coronavirus (SARS-CoV) spike protein amino acids 318-510 (S318-510) containing the receptor-binding domain. The S protein fragment was purified from the culture supernatant of stably transformed HEK293T cells secreting a tagged version of the protein. The vaccine was given subcutaneously to 129S6/SvEv mice in saline, with alum adjuvant or with alum plus CpG oligodeoxynucleotides (ODN). Mice immunized with the adjuvanted antigen elicited strong antibody and cellular immune responses; furthermore, adding the CpG ODN to the alum resulted in increased IgG2a antibody titers and a higher number of INF-γ-secreting murine splenocytes. Mice vaccinated with S318-510 deglycosylated by PNGase F (dgS318-510) showed a lower neutralizing antibody response but had similar numbers of INF-γ-producing cells in the spleen. This finding suggests that carbohydrate is important for the immunogenicity of the S318-510 protein fragment and provide useful information for designing an effective and safe SARS subunit vaccine.


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<s3>CAN</s3>
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<sZ>6 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
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<wicri:noRegion>Saskatoon, Sask., S7N 5E3</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Petric, Martin" sort="Petric, Martin" uniqKey="Petric M" first="Martin" last="Petric">Martin Petric</name>
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<s1>University of British Columbia Centre for Disease Control</s1>
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<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>University of British Columbia Centre for Disease Control</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="See, Raymond H" sort="See, Raymond H" uniqKey="See R" first="Raymond H." last="See">Raymond H. See</name>
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<sZ>8 aut.</sZ>
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</inist:fA14>
<country>Canada</country>
<wicri:noRegion>University of British Columbia Centre for Disease Control</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Brunham, Robert C" sort="Brunham, Robert C" uniqKey="Brunham R" first="Robert C." last="Brunham">Robert C. Brunham</name>
<affiliation wicri:level="1">
<inist:fA14 i1="04">
<s1>University of British Columbia Centre for Disease Control</s1>
<s2>Vancouver, BC, V5Z 4R4</s2>
<s3>CAN</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>University of British Columbia Centre for Disease Control</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Finlay, B Brett" sort="Finlay, B Brett" uniqKey="Finlay B" first="B. Brett" last="Finlay">B. Brett Finlay</name>
<affiliation wicri:level="1">
<inist:fA14 i1="05">
<s1>Michael Smith Laboratories and Departments of Biochemistry and Molecular Biology and Microbiology and Immunology, University of British Columbia</s1>
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<s3>CAN</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Vancouver, BC, V6T 1Z3</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cameron, Cheryl" sort="Cameron, Cheryl" uniqKey="Cameron C" first="Cheryl" last="Cameron">Cheryl Cameron</name>
<affiliation wicri:level="1">
<inist:fA14 i1="06">
<s1>Division of Experimental Therapeutics, University Health Network, Toronto General Research Institute</s1>
<s2>Toronto, Ont</s2>
<s3>CAN</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Toronto, Ont</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name>
<affiliation wicri:level="1">
<inist:fA14 i1="06">
<s1>Division of Experimental Therapeutics, University Health Network, Toronto General Research Institute</s1>
<s2>Toronto, Ont</s2>
<s3>CAN</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Toronto, Ont</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cochrane, Alan" sort="Cochrane, Alan" uniqKey="Cochrane A" first="Alan" last="Cochrane">Alan Cochrane</name>
<affiliation wicri:level="4">
<inist:fA14 i1="02">
<s1>Departments of Molecular and Medical Genetics and Microbiology, University of Toronto</s1>
<s2>Ont., M5S 1A8</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
<orgName type="university">Université de Toronto</orgName>
</affiliation>
</author>
<author>
<name sortKey="Rini, James M" sort="Rini, James M" uniqKey="Rini J" first="James M." last="Rini">James M. Rini</name>
<affiliation wicri:level="4">
<inist:fA14 i1="02">
<s1>Departments of Molecular and Medical Genetics and Microbiology, University of Toronto</s1>
<s2>Ont., M5S 1A8</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
<orgName type="university">Université de Toronto</orgName>
</affiliation>
<affiliation wicri:level="4">
<inist:fA14 i1="03">
<s1>Department of Biochemistry, University of Toronto</s1>
<s2>Ont., M5S 1A8</s2>
<s3>CAN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
<orgName type="university">Université de Toronto</orgName>
</affiliation>
</author>
<author>
<name sortKey="Babiuk, Lorne A" sort="Babiuk, Lorne A" uniqKey="Babiuk L" first="Lorne A." last="Babiuk">Lorne A. Babiuk</name>
<affiliation wicri:level="1">
<inist:fA14 i1="01">
<s1>Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, 120 Veterinary Road</s1>
<s2>Saskatoon, Sask., S7N 5E3</s2>
<s3>CAN</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Canada</country>
<wicri:noRegion>Saskatoon, Sask., S7N 5E3</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">Vaccine</title>
<title level="j" type="abbreviated">Vaccine</title>
<idno type="ISSN">0264-410X</idno>
<imprint>
<date when="2007">2007</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">Vaccine</title>
<title level="j" type="abbreviated">Vaccine</title>
<idno type="ISSN">0264-410X</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Alum Compounds</term>
<term>Animals</term>
<term>Antibodies, Viral (blood)</term>
<term>Cell Line</term>
<term>Female</term>
<term>Humans</term>
<term>Immunogenicity</term>
<term>Interferon-gamma (biosynthesis)</term>
<term>Membrane Glycoproteins (chemistry)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Mice</term>
<term>Mouse</term>
<term>Oligodeoxyribonucleotides</term>
<term>Protein</term>
<term>Receptors, Virus (metabolism)</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 virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Subunit</term>
<term>Vaccine</term>
<term>Viral Envelope Proteins (chemistry)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
<term>Viral Vaccines (administration & dosage)</term>
<term>Viral Vaccines (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Alun</term>
<term>Animaux</term>
<term>Anticorps antiviraux (sang)</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires ()</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains</term>
<term>Interféron gamma (biosynthèse)</term>
<term>Lignée cellulaire</term>
<term>Oligodésoxyribonucléotides</term>
<term>Protéines de l'enveloppe virale ()</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Souris</term>
<term>Syndrome respiratoire aigu sévère ()</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Vaccins antiviraux (administration et posologie)</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Virus du SRAS (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en">
<term>Interferon-gamma</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Membrane Glycoproteins</term>
<term>Receptors, Virus</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en">
<term>Alum Compounds</term>
<term>Oligodeoxyribonucleotides</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr">
<term>Vaccins antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr">
<term>Interféron gamma</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Vaccins antiviraux</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="métabolisme" xml:lang="fr">
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Récepteurs viraux</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>Animals</term>
<term>Cell Line</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Alun</term>
<term>Animaux</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Oligodésoxyribonucléotides</term>
<term>Protéines de l'enveloppe virale</term>
<term>Souris</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Souris</term>
<term>Immunogénicité</term>
<term>Protéine</term>
<term>Sousunité</term>
<term>Vaccin</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Vaccin</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">We studied the immunogenicity of an anti-SARS subunit vaccine comprised of the fragment of the SARS coronavirus (SARS-CoV) spike protein amino acids 318-510 (S318-510) containing the receptor-binding domain. The S protein fragment was purified from the culture supernatant of stably transformed HEK293T cells secreting a tagged version of the protein. The vaccine was given subcutaneously to 129S6/SvEv mice in saline, with alum adjuvant or with alum plus CpG oligodeoxynucleotides (ODN). Mice immunized with the adjuvanted antigen elicited strong antibody and cellular immune responses; furthermore, adding the CpG ODN to the alum resulted in increased IgG2a antibody titers and a higher number of INF-γ-secreting murine splenocytes. Mice vaccinated with S318-510 deglycosylated by PNGase F (dgS318-510) showed a lower neutralizing antibody response but had similar numbers of INF-γ-producing cells in the spleen. This finding suggests that carbohydrate is important for the immunogenicity of the S318-510 protein fragment and provide useful information for designing an effective and safe SARS subunit vaccine.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Canada</li>
</country>
<region>
<li>Ontario</li>
</region>
<settlement>
<li>Toronto</li>
</settlement>
<orgName>
<li>Université de Toronto</li>
</orgName>
</list>
<tree>
<country name="Canada">
<noRegion>
<name sortKey="Zakhartchouk, Alexander N" sort="Zakhartchouk, Alexander N" uniqKey="Zakhartchouk A" first="Alexander N." last="Zakhartchouk">Alexander N. Zakhartchouk</name>
</noRegion>
<name sortKey="Auperin, Thierry" sort="Auperin, Thierry" uniqKey="Auperin T" first="Thierry" last="Auperin">Thierry Auperin</name>
<name sortKey="Auperin, Thierry" sort="Auperin, Thierry" uniqKey="Auperin T" first="Thierry" last="Auperin">Thierry 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="Cameron, Cheryl" sort="Cameron, Cheryl" uniqKey="Cameron C" first="Cheryl" last="Cameron">Cheryl Cameron</name>
<name sortKey="Cochrane, Alan" sort="Cochrane, Alan" uniqKey="Cochrane A" first="Alan" last="Cochrane">Alan Cochrane</name>
<name sortKey="Finlay, B Brett" sort="Finlay, B Brett" uniqKey="Finlay B" first="B. Brett" last="Finlay">B. Brett Finlay</name>
<name sortKey="Kelvin, David J" sort="Kelvin, David J" uniqKey="Kelvin D" first="David J." last="Kelvin">David J. Kelvin</name>
<name sortKey="Mutwiri, George" sort="Mutwiri, George" uniqKey="Mutwiri G" first="George" last="Mutwiri">George Mutwiri</name>
<name sortKey="Petric, Martin" sort="Petric, Martin" uniqKey="Petric M" first="Martin" last="Petric">Martin Petric</name>
<name sortKey="Rini, James M" sort="Rini, James M" uniqKey="Rini J" first="James M." last="Rini">James M. Rini</name>
<name sortKey="Rini, James M" sort="Rini, James M" uniqKey="Rini J" first="James M." last="Rini">James M. Rini</name>
<name sortKey="Satkunarajah, Malathy" sort="Satkunarajah, Malathy" uniqKey="Satkunarajah M" first="Malathy" last="Satkunarajah">Malathy Satkunarajah</name>
<name sortKey="Satkunarajah, Malathy" sort="Satkunarajah, Malathy" uniqKey="Satkunarajah M" first="Malathy" last="Satkunarajah">Malathy Satkunarajah</name>
<name sortKey="See, Raymond H" sort="See, Raymond H" uniqKey="See R" first="Raymond H." last="See">Raymond H. See</name>
<name sortKey="Sharon, Chetna" sort="Sharon, Chetna" uniqKey="Sharon C" first="Chetna" last="Sharon">Chetna Sharon</name>
<name sortKey="Sharon, Chetna" sort="Sharon, Chetna" uniqKey="Sharon C" first="Chetna" last="Sharon">Chetna Sharon</name>
<name sortKey="Viswanathan, Sathiyanarayanan" sort="Viswanathan, Sathiyanarayanan" uniqKey="Viswanathan S" first="Sathiyanarayanan" last="Viswanathan">Sathiyanarayanan Viswanathan</name>
</country>
</tree>
</affiliations>
</record>

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