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Efficient induction of cytotoxic T lymphocytes specific for severe acute respiratory syndrome (SARS)-associated coronavirus by immunization with surface-linked liposomal peptides derived from a non-structural polyprotein 1a.

Identifieur interne : 002B31 ( Main/Curation ); précédent : 002B30; suivant : 002B32

Efficient induction of cytotoxic T lymphocytes specific for severe acute respiratory syndrome (SARS)-associated coronavirus by immunization with surface-linked liposomal peptides derived from a non-structural polyprotein 1a.

Auteurs : Shunsuke Kohyama [Japon] ; Satoshi Ohno ; Tatsuya Suda ; Maiko Taneichi ; Shoichi Yokoyama ; Masahito Mori ; Akiharu Kobayashi ; Hidenori Hayashi ; Tetsuya Uchida ; Masanori Matsui

Source :

RBID : pubmed:19748524

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English descriptors

Abstract

Spike and nucleocapsid are structural proteins of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) and major targets for cytotoxic T lymphocytes (CTLs). In contrast, non-structural proteins encoded by two-thirds of viral genome are poorly characterized for cell-mediated immunity. We previously demonstrated that nucleocapsid-derived peptides chemically coupled to the surface of liposomes effectively elicited SARS-CoV-specific CTLs in mice. Here, we attempted to identify HLA-A*0201-restricted CTL epitopes derived from a non-structural polyprotein 1a (pp1a) of SARS-CoV, and investigated whether liposomal peptides derived from pp1a were effective for CTL induction. Out of 30 peptides predicted on computational algorithms, nine peptides could significantly induce interferon gamma (IFN-gamma)-producing CD8(+) T cells in mice. These peptides were coupled to the surface of liposomes, and inoculated into mice. Six liposomal peptides effectively induced IFN-gamma-producing CD8(+) T cells and seven liposomal peptides including the six peptides primed CTLs showing in vivo killing activities. Further, CTLs induced by the seven liposomal peptides lysed an HLA-A*0201 positive cell line expressing naturally processed, pp1a-derived peptides. Of note, one of the liposomal peptides induced high numbers of long-lasting memory CTLs. These data suggest that surface-linked liposomal peptides derived from pp1a might offer an efficient CTL-based vaccine against SARS.

DOI: 10.1016/j.antiviral.2009.09.004
PubMed: 19748524

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<name sortKey="Taneichi, Maiko" sort="Taneichi, Maiko" uniqKey="Taneichi M" first="Maiko" last="Taneichi">Maiko Taneichi</name>
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<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Base Sequence</term>
<term>Cell Line</term>
<term>Epitopes, T-Lymphocyte (chemistry)</term>
<term>Humans</term>
<term>Immunization</term>
<term>Liposomes (administration & dosage)</term>
<term>Liposomes (chemistry)</term>
<term>Liposomes (immunology)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Molecular Sequence Data</term>
<term>Peptides (administration & dosage)</term>
<term>Peptides (chemistry)</term>
<term>Peptides (immunology)</term>
<term>RNA Replicase (chemistry)</term>
<term>RNA Replicase (immunology)</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 (virology)</term>
<term>T-Lymphocytes, Cytotoxic (chemistry)</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
<term>Viral Nonstructural Proteins (chemistry)</term>
<term>Viral Nonstructural Proteins (immunology)</term>
<term>Viral Vaccines</term>
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<term>Animaux</term>
<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T ()</term>
<term>Humains</term>
<term>Immunisation</term>
<term>Lignée cellulaire</term>
<term>Liposomes ()</term>
<term>Liposomes (administration et posologie)</term>
<term>Liposomes (immunologie)</term>
<term>Lymphocytes T cytotoxiques ()</term>
<term>Lymphocytes T cytotoxiques (immunologie)</term>
<term>Peptides ()</term>
<term>Peptides (administration et posologie)</term>
<term>Peptides (immunologie)</term>
<term>Protéines virales non structurales ()</term>
<term>Protéines virales non structurales (immunologie)</term>
<term>RNA replicase ()</term>
<term>RNA replicase (immunologie)</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Syndrome respiratoire aigu sévère ()</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
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<term>Peptides</term>
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<term>Epitopes, T-Lymphocyte</term>
<term>Liposomes</term>
<term>Peptides</term>
<term>RNA Replicase</term>
<term>Viral Nonstructural Proteins</term>
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<term>Liposomes</term>
<term>Peptides</term>
<term>RNA Replicase</term>
<term>Viral Nonstructural Proteins</term>
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<term>Liposomes</term>
<term>Peptides</term>
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<term>T-Lymphocytes, Cytotoxic</term>
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<term>Liposomes</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Peptides</term>
<term>Protéines virales non structurales</term>
<term>RNA replicase</term>
<term>Syndrome respiratoire aigu sévère</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>T-Lymphocytes, Cytotoxic</term>
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<term>Severe Acute Respiratory Syndrome</term>
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<term>Syndrome respiratoire aigu sévère</term>
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<term>Severe Acute Respiratory Syndrome</term>
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<term>Amino Acid Sequence</term>
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<term>Base Sequence</term>
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<term>Humans</term>
<term>Immunization</term>
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<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T</term>
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<term>Immunisation</term>
<term>Lignée cellulaire</term>
<term>Liposomes</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Peptides</term>
<term>Protéines virales non structurales</term>
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<term>Souris</term>
<term>Souris transgéniques</term>
<term>Syndrome respiratoire aigu sévère</term>
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<front>
<div type="abstract" xml:lang="en">Spike and nucleocapsid are structural proteins of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) and major targets for cytotoxic T lymphocytes (CTLs). In contrast, non-structural proteins encoded by two-thirds of viral genome are poorly characterized for cell-mediated immunity. We previously demonstrated that nucleocapsid-derived peptides chemically coupled to the surface of liposomes effectively elicited SARS-CoV-specific CTLs in mice. Here, we attempted to identify HLA-A*0201-restricted CTL epitopes derived from a non-structural polyprotein 1a (pp1a) of SARS-CoV, and investigated whether liposomal peptides derived from pp1a were effective for CTL induction. Out of 30 peptides predicted on computational algorithms, nine peptides could significantly induce interferon gamma (IFN-gamma)-producing CD8(+) T cells in mice. These peptides were coupled to the surface of liposomes, and inoculated into mice. Six liposomal peptides effectively induced IFN-gamma-producing CD8(+) T cells and seven liposomal peptides including the six peptides primed CTLs showing in vivo killing activities. Further, CTLs induced by the seven liposomal peptides lysed an HLA-A*0201 positive cell line expressing naturally processed, pp1a-derived peptides. Of note, one of the liposomal peptides induced high numbers of long-lasting memory CTLs. These data suggest that surface-linked liposomal peptides derived from pp1a might offer an efficient CTL-based vaccine against SARS.</div>
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