Immune responses to T-cell epitopes of SARS CoV-N protein are enhanced by N immunization with a chimera of lysosome-associated membrane protein
Identifieur interne : 000813 ( PascalFrancis/Curation ); précédent : 000812; suivant : 000814Immune responses to T-cell epitopes of SARS CoV-N protein are enhanced by N immunization with a chimera of lysosome-associated membrane protein
Auteurs : K. Yang [États-Unis, République populaire de Chine] ; K. Sun [Singapour] ; K. N. Srinivasan [États-Unis, Singapour] ; J. Salmon [États-Unis] ; E. T. Marques [États-Unis] ; J. Xu [République populaire de Chine] ; J. T. August [États-Unis]Source :
- Gene therapy : (Basingstoke) [ 0969-7128 ] ; 2009.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
In our previous study by Gupta et al, dominant T-cell epitopes of SARS CoV-N(N) protein were predicted by software. The spectrum of interferon (IFN)-γ responses of Balb/c mice immunized against two different forms of SARS CoV-N plasmid was then analyzed. A cluster of dominant T-cell epitopes of SARS CoV-N protein was found in the N-terminus (amino acids 76-114). On the basis of this study, four different plasmids were constructed: (i) DNA encoding the unmodified N (p-N) or N70-122 (p-N70-122) as an endogenous cytoplasmic protein or (ii) DNA encoding a lysosome-associated membrane protein (LAMP) chimera with N (p-LAMP/N) or N70-122 (p-LAMP/N70-122). The immune responses of mice to these four constructs were evaluated. The results showed marked differences in the responses of the immunized mice. A single priming immunization with the p-LAMP/N construct was sufficient to elicit an antibody response. Enzyme-linked immunospot (ELISpot) assay indicated that p-LAMP/N70-122 and p-LAMP/N plasmids both elicited a greater IFN-γ response than p-N. p-N and p-N70-122 constructs induced low or undetectable levels of cytokine secretion. We also found that the p-LAMP/N70-122 construct promoted a long-lasting T-cell memory response without an additional boost 6 months after three immunizations. These findings show that DNA vaccines, even epitope-based DNA vaccines using LAMP as chimera, can elicit both humoral and cellular immune responses.
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Xu</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Neurology, Tangdu Hospital, The Fourth Military Medical University</s1><s2>Xi'an, Shaanxi Province</s2><s3>CHN</s3><sZ>6 aut.</sZ></inist:fA14><country>République populaire de Chine</country></affiliation></author><author><name sortKey="August, J T" sort="August, J T" uniqKey="August J" first="J. T." last="August">J. T. August</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">09-0476528</idno><date when="2009">2009</date><idno type="stanalyst">PASCAL 09-0476528 INIST</idno><idno type="RBID">Pascal:09-0476528</idno><idno type="wicri:Area/PascalFrancis/Corpus">000175</idno><idno type="wicri:Area/PascalFrancis/Curation">000813</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Immune responses to T-cell epitopes of SARS CoV-N protein are enhanced by N immunization with a chimera of lysosome-associated membrane protein</title><author><name sortKey="Yang, K" sort="Yang, K" uniqKey="Yang K" first="K." last="Yang">K. Yang</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Immunology, The Fourth Military Medical University</s1><s2>Xi'an, Shaanxi Province</s2><s3>CHN</s3><sZ>1 aut.</sZ></inist:fA14><country>République populaire de Chine</country></affiliation></author><author><name sortKey="Sun, K" sort="Sun, K" uniqKey="Sun K" first="K." last="Sun">K. Sun</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Biomedical Sciences, Johns Hopkins in Singapore</s1><s3>SGP</s3><sZ>2 aut.</sZ></inist:fA14><country>Singapour</country></affiliation></author><author><name sortKey="Srinivasan, K N" sort="Srinivasan, K N" uniqKey="Srinivasan K" first="K. N." last="Srinivasan">K. N. Srinivasan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Product Evaluation and Registration Division, Centre for Drug Administration, Health Sciences Authority</s1><s3>SGP</s3><sZ>3 aut.</sZ></inist:fA14><country>Singapour</country></affiliation></author><author><name sortKey="Salmon, J" sort="Salmon, J" uniqKey="Salmon J" first="J." last="Salmon">J. Salmon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Marques, E T" sort="Marques, E T" uniqKey="Marques E" first="E. T." last="Marques">E. T. Marques</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Division of Infectious Diseases, Department of Medicine, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Xu, J" sort="Xu, J" uniqKey="Xu J" first="J." last="Xu">J. Xu</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Neurology, Tangdu Hospital, The Fourth Military Medical University</s1><s2>Xi'an, Shaanxi Province</s2><s3>CHN</s3><sZ>6 aut.</sZ></inist:fA14><country>République populaire de Chine</country></affiliation></author><author><name sortKey="August, J T" sort="August, J T" uniqKey="August J" first="J. T." last="August">J. T. August</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></analytic><series><title level="j" type="main">Gene therapy : (Basingstoke)</title><title level="j" type="abbreviated">Gene ther. : (Basingstoke)</title><idno type="ISSN">0969-7128</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Gene therapy : (Basingstoke)</title><title level="j" type="abbreviated">Gene ther. : (Basingstoke)</title><idno type="ISSN">0969-7128</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigenic determinant</term><term>Chimera</term><term>Gene therapy</term><term>Genetic vaccine</term><term>Immune response</term><term>Immunization</term><term>Lamp</term><term>Lysosome</term><term>Membrane protein</term><term>Severe acute respiratory syndrome virus</term><term>T-Lymphocyte</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Réponse immune</term><term>Lymphocyte T</term><term>Déterminant antigénique</term><term>Protéine membranaire</term><term>Immunisation</term><term>Chimère</term><term>Lysosome</term><term>Lampe</term><term>Vaccin génétique</term><term>Thérapie génique</term><term>Virus syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In our previous study by Gupta et al, dominant T-cell epitopes of SARS CoV-N(N) protein were predicted by software. The spectrum of interferon (IFN)-γ responses of Balb/c mice immunized against two different forms of SARS CoV-N plasmid was then analyzed. A cluster of dominant T-cell epitopes of SARS CoV-N protein was found in the N-terminus (amino acids 76-114). On the basis of this study, four different plasmids were constructed: (i) DNA encoding the unmodified N (p-N) or N<sub>70-122</sub> (p-N<sub>70-122</sub>) as an endogenous cytoplasmic protein or (ii) DNA encoding a lysosome-associated membrane protein (LAMP) chimera with N (p-LAMP/N) or N<sub>70-122</sub> (p-LAMP/N<sub>70-122</sub>). The immune responses of mice to these four constructs were evaluated. The results showed marked differences in the responses of the immunized mice. A single priming immunization with the p-LAMP/N construct was sufficient to elicit an antibody response. Enzyme-linked immunospot (ELISpot) assay indicated that p-LAMP/N<sub>70-122</sub> and p-LAMP/N plasmids both elicited a greater IFN-γ response than p-N. p-N and p-N<sub>70-122</sub> constructs induced low or undetectable levels of cytokine secretion. We also found that the p-LAMP/N<sub>70-122</sub> construct promoted a long-lasting T-cell memory response without an additional boost 6 months after three immunizations. These findings show that DNA vaccines, even epitope-based DNA vaccines using LAMP as chimera, can elicit both humoral and cellular immune responses.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0969-7128</s0></fA01><fA03 i2="1"><s0>Gene ther. : (Basingstoke)</s0></fA03><fA05><s2>16</s2></fA05><fA06><s2>11</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Immune responses to T-cell epitopes of SARS CoV-N protein are enhanced by N immunization with a chimera of lysosome-associated membrane protein</s1></fA08><fA11 i1="01" i2="1"><s1>YANG (K.)</s1></fA11><fA11 i1="02" i2="1"><s1>SUN (K.)</s1></fA11><fA11 i1="03" i2="1"><s1>SRINIVASAN (K. N.)</s1></fA11><fA11 i1="04" i2="1"><s1>SALMON (J.)</s1></fA11><fA11 i1="05" i2="1"><s1>MARQUES (E. T.)</s1></fA11><fA11 i1="06" i2="1"><s1>XU (J.)</s1></fA11><fA11 i1="07" i2="1"><s1>AUGUST (J. T.)</s1></fA11><fA14 i1="01"><s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Immunology, The Fourth Military Medical University</s1><s2>Xi'an, Shaanxi Province</s2><s3>CHN</s3><sZ>1 aut.</sZ></fA14><fA14 i1="03"><s1>Division of Biomedical Sciences, Johns Hopkins in Singapore</s1><s3>SGP</s3><sZ>2 aut.</sZ></fA14><fA14 i1="04"><s1>Product Evaluation and Registration Division, Centre for Drug Administration, Health Sciences Authority</s1><s3>SGP</s3><sZ>3 aut.</sZ></fA14><fA14 i1="05"><s1>Division of Infectious Diseases, Department of Medicine, The Johns Hopkins University School of Medicine</s1><s2>Baltimore, MD</s2><s3>USA</s3><sZ>5 aut.</sZ></fA14><fA14 i1="06"><s1>Department of Neurology, Tangdu Hospital, The Fourth Military Medical University</s1><s2>Xi'an, Shaanxi Province</s2><s3>CHN</s3><sZ>6 aut.</sZ></fA14><fA20><s1>1353-1362</s1></fA20><fA21><s1>2009</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>26274</s2><s5>354000170372360090</s5></fA43><fA44><s0>0000</s0><s1>© 2009 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>41 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>09-0476528</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Gene therapy : (Basingstoke)</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>In our previous study by Gupta et al, dominant T-cell epitopes of SARS CoV-N(N) protein were predicted by software. The spectrum of interferon (IFN)-γ responses of Balb/c mice immunized against two different forms of SARS CoV-N plasmid was then analyzed. A cluster of dominant T-cell epitopes of SARS CoV-N protein was found in the N-terminus (amino acids 76-114). On the basis of this study, four different plasmids were constructed: (i) DNA encoding the unmodified N (p-N) or N<sub>70-122</sub> (p-N<sub>70-122</sub>) as an endogenous cytoplasmic protein or (ii) DNA encoding a lysosome-associated membrane protein (LAMP) chimera with N (p-LAMP/N) or N<sub>70-122</sub> (p-LAMP/N<sub>70-122</sub>). The immune responses of mice to these four constructs were evaluated. The results showed marked differences in the responses of the immunized mice. A single priming immunization with the p-LAMP/N construct was sufficient to elicit an antibody response. Enzyme-linked immunospot (ELISpot) assay indicated that p-LAMP/N<sub>70-122</sub> and p-LAMP/N plasmids both elicited a greater IFN-γ response than p-N. p-N and p-N<sub>70-122</sub> constructs induced low or undetectable levels of cytokine secretion. We also found that the p-LAMP/N<sub>70-122</sub> construct promoted a long-lasting T-cell memory response without an additional boost 6 months after three immunizations. These findings show that DNA vaccines, even epitope-based DNA vaccines using LAMP as chimera, can elicit both humoral and cellular immune responses.</s0></fC01><fC02 i1="01" i2="X"><s0>002A31D01D</s0></fC02><fC02 i1="02" i2="X"><s0>002B27D03</s0></fC02><fC02 i1="03" i2="X"><s0>215</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Réponse immune</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Immune response</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Respuesta inmune</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Lymphocyte T</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>T-Lymphocyte</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Linfocito T</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Déterminant antigénique</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Antigenic determinant</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Determinante antigénico</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Protéine membranaire</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Membrane protein</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Proteína membranar</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Immunisation</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Immunization</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Inmunización</s0><s5>05</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Chimère</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Chimera</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Quimera</s0><s5>06</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Lysosome</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Lysosome</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Lisosoma</s0><s5>07</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Lampe</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Lamp</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Lámpara</s0><s5>08</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Vaccin génétique</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Genetic vaccine</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Vacuna genética</s0><s5>09</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Thérapie génique</s0><s5>10</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Gene therapy</s0><s5>10</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Terapia génica</s0><s5>10</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Virus syndrome respiratoire aigu sévère</s0><s2>NW</s2><s5>16</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Severe acute respiratory syndrome virus</s0><s2>NW</s2><s5>16</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Severe acute respiratory syndrome virus</s0><s2>NW</s2><s5>16</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fN21><s1>348</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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|wiki= Sante
|area= SrasV1
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|texte= Immune responses to T-cell epitopes of SARS CoV-N protein are enhanced by N immunization with a chimera of lysosome-associated membrane protein
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