Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates
Identifieur interne : 001005 ( Main/Exploration ); précédent : 001004; suivant : 001006Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates
Auteurs : Qidi Wang [République populaire de Chine] ; Lianfeng Zhang [République populaire de Chine] ; Kazuhiko Kuwahara [Japon] ; Li Li [République populaire de Chine] ; Zijie Liu [République populaire de Chine] ; Taisheng Li [République populaire de Chine] ; Hua Zhu [République populaire de Chine] ; Jiangning Liu [République populaire de Chine] ; Yanfeng Xu [République populaire de Chine] ; Jing Xie [République populaire de Chine] ; Hiroshi Morioka [Japon] ; Nobuo Sakaguchi [Japon] ; Chuan Qin [République populaire de Chine] ; Gang Liu [République populaire de Chine]Source :
- ACS Infectious Diseases [ 2373-8227 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps neutralisants (immunologie), Déterminants antigéniques des lymphocytes B (), Déterminants antigéniques des lymphocytes B (immunologie), Facilitation dépendante des anticorps, Glycoprotéine de spicule des coronavirus (), Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (immunologie), Humains, Macaca mulatta, Modèles animaux de maladie humaine, Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (), Virus du SRAS (génétique), Virus du SRAS (immunologie), Épitopes immunodominants (), Épitopes immunodominants (génétique), Épitopes immunodominants (immunologie).
- MESH :
- génétique : Glycoprotéine de spicule des coronavirus, Virus du SRAS, Épitopes immunodominants.
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Déterminants antigéniques des lymphocytes B, Glycoprotéine de spicule des coronavirus, Syndrome respiratoire aigu sévère, Virus du SRAS, Épitopes immunodominants.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Déterminants antigéniques des lymphocytes B, Facilitation dépendante des anticorps, Glycoprotéine de spicule des coronavirus, Humains, Macaca mulatta, Modèles animaux de maladie humaine, Virus du SRAS, Épitopes immunodominants.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Antibody-Dependent Enhancement, Disease Models, Animal, Epitopes, B-Lymphocyte (chemistry), Epitopes, B-Lymphocyte (immunology), Humans, Immunodominant Epitopes (chemistry), Immunodominant Epitopes (genetics), Immunodominant Epitopes (immunology), Macaca mulatta, SARS Virus (chemistry), SARS Virus (genetics), SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (virology), Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology).
- MESH :
- chemical , chemistry : Epitopes, B-Lymphocyte, Immunodominant Epitopes, Spike Glycoprotein, Coronavirus.
- chemical , genetics : Immunodominant Epitopes, Spike Glycoprotein, Coronavirus.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Epitopes, B-Lymphocyte, Immunodominant Epitopes, Spike Glycoprotein, Coronavirus.
- chemistry : SARS Virus.
- genetics : SARS Virus.
- immunology : SARS Virus, Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Animals, Antibody-Dependent Enhancement, Disease Models, Animal, Humans, Macaca mulatta.
Abstract
Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S471–503, S604–625, and S1164–1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S597–603 induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S597–603 and S604–625) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S597–603 epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection.
Url:
DOI: 10.1021/acsinfecdis.6b00006
PubMed: 27627203
PubMed Central: 7075522
Affiliations:
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Le document en format XML
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Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Tsinghua-Peking Center for Life Sciences & School of Pharmaceutical Sciences,<institution>Tsinghua University</institution>, Haidian District, Beijing 100084,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Materia Medica,<institution>Chinese Academy of Medical Sciences & Peking Union Medical College</institution>, 2A Nanwei Road, Xuanwu District, Beijing 100050,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country 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Elicited both Enhancing and Neutralizing Effects on Infection in Non-human
Primates</title><author><name sortKey="Wang, Qidi" sort="Wang, Qidi" uniqKey="Wang Q" first="Qidi" last="Wang">Qidi Wang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Materia Medica,<institution>Chinese Academy of Medical Sciences & Peking Union Medical College</institution>, 2A Nanwei Road, Xuanwu District, Beijing 100050,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Lianfeng" sort="Zhang, Lianfeng" uniqKey="Zhang L" first="Lianfeng" last="Zhang">Lianfeng Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff3">Institute of Laboratory Animal Science,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100021,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kuwahara, Kazuhiko" sort="Kuwahara, Kazuhiko" uniqKey="Kuwahara K" first="Kazuhiko" last="Kuwahara">Kazuhiko Kuwahara</name><affiliation wicri:level="1"><nlm:aff id="aff4">Faculty of Life Sciences,<institution>Kumamoto University</institution>, 1-1-1 Honjo, Kumamoto 860-8556,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name><affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Materia Medica,<institution>Chinese Academy of Medical Sciences & Peking Union Medical College</institution>, 2A Nanwei Road, Xuanwu District, Beijing 100050,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Zijie" sort="Liu, Zijie" uniqKey="Liu Z" first="Zijie" last="Liu">Zijie Liu</name><affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Materia Medica,<institution>Chinese Academy of Medical Sciences & Peking Union Medical College</institution>, 2A Nanwei Road, Xuanwu District, Beijing 100050,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Taisheng" sort="Li, Taisheng" uniqKey="Li T" first="Taisheng" last="Li">Taisheng Li</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Infectious Disease, Peking Union Medical College Hospital and AIDS Research Center,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100071,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhu, Hua" sort="Zhu, Hua" uniqKey="Zhu H" first="Hua" last="Zhu">Hua Zhu</name><affiliation wicri:level="1"><nlm:aff id="aff3">Institute of Laboratory Animal Science,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100021,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Jiangning" sort="Liu, Jiangning" uniqKey="Liu J" first="Jiangning" last="Liu">Jiangning Liu</name><affiliation wicri:level="1"><nlm:aff id="aff3">Institute of Laboratory Animal Science,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100021,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Yanfeng" sort="Xu, Yanfeng" uniqKey="Xu Y" first="Yanfeng" last="Xu">Yanfeng Xu</name><affiliation wicri:level="1"><nlm:aff id="aff3">Institute of Laboratory Animal Science,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100021,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xie, Jing" sort="Xie, Jing" uniqKey="Xie J" first="Jing" last="Xie">Jing Xie</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Infectious Disease, Peking Union Medical College Hospital and AIDS Research Center,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100071,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Morioka, Hiroshi" sort="Morioka, Hiroshi" uniqKey="Morioka H" first="Hiroshi" last="Morioka">Hiroshi Morioka</name><affiliation wicri:level="1"><nlm:aff id="aff4">Faculty of Life Sciences,<institution>Kumamoto University</institution>, 1-1-1 Honjo, Kumamoto 860-8556,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sakaguchi, Nobuo" sort="Sakaguchi, Nobuo" uniqKey="Sakaguchi N" first="Nobuo" last="Sakaguchi">Nobuo Sakaguchi</name><affiliation wicri:level="1"><nlm:aff id="aff4">Faculty of Life Sciences,<institution>Kumamoto University</institution>, 1-1-1 Honjo, Kumamoto 860-8556,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">WPI Immunology Frontier Research Center,<institution>Osaka University</institution>, 3-1 Yamada-oka, Suita, Osaka 565-0871,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><affiliation wicri:level="1"><nlm:aff id="aff3">Institute of Laboratory Animal Science,<institution>Chinese Academy of Medical Sciences and Peking Union Medical College</institution>, Beijing 100021,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Tsinghua-Peking Center for Life Sciences & School of Pharmaceutical Sciences,<institution>Tsinghua University</institution>, Haidian District, Beijing 100084,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Institute of Materia Medica,<institution>Chinese Academy of Medical Sciences & Peking Union Medical College</institution>, 2A Nanwei Road, Xuanwu District, Beijing 100050,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">ACS Infectious Diseases</title><idno type="eISSN">2373-8227</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Viral (immunology)</term><term>Antibody-Dependent Enhancement</term><term>Disease Models, Animal</term><term>Epitopes, B-Lymphocyte (chemistry)</term><term>Epitopes, B-Lymphocyte (immunology)</term><term>Humans</term><term>Immunodominant Epitopes (chemistry)</term><term>Immunodominant Epitopes (genetics)</term><term>Immunodominant Epitopes (immunology)</term><term>Macaca mulatta</term><term>SARS Virus (chemistry)</term><term>SARS Virus (genetics)</term><term>SARS Virus (immunology)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Spike Glycoprotein, Coronavirus (chemistry)</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Déterminants antigéniques des lymphocytes B ()</term><term>Déterminants antigéniques des lymphocytes B (immunologie)</term><term>Facilitation dépendante des anticorps</term><term>Glycoprotéine de spicule des coronavirus ()</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Glycoprotéine de spicule des coronavirus (immunologie)</term><term>Humains</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Virus du SRAS ()</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (immunologie)</term><term>Épitopes immunodominants ()</term><term>Épitopes immunodominants (génétique)</term><term>Épitopes immunodominants (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Epitopes, B-Lymphocyte</term><term>Immunodominant Epitopes</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Immunodominant Epitopes</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Epitopes, B-Lymphocyte</term><term>Immunodominant Epitopes</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term><term>Virus du SRAS</term><term>Épitopes immunodominants</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Déterminants antigéniques des lymphocytes B</term><term>Glycoprotéine de spicule des coronavirus</term><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term><term>Épitopes immunodominants</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="virologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Antibody-Dependent Enhancement</term><term>Disease Models, Animal</term><term>Humans</term><term>Macaca mulatta</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Déterminants antigéniques des lymphocytes B</term><term>Facilitation dépendante des anticorps</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term><term>Virus du SRAS</term><term>Épitopes immunodominants</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="id6b00006_0011" id="ab-tgr1"></graphic></p><p>Severe
acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV)
and has the potential to threaten global public health and socioeconomic
stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV
infection in vitro and in non-human primates clouds the prospects
for a safe vaccine. Using antibodies from SARS patients, we identified
and characterized SARS-CoV B-cell peptide epitopes with disparate
functions. In rhesus macaques, the spike glycoprotein peptides S<sub>471–503</sub>, S<sub>604–625</sub>, and S<sub>1164–1191</sub> elicited antibodies that efficiently prevented infection in non-human
primates. In contrast, peptide S<sub>597–603</sub> induced
antibodies that enhanced infection both in vitro and in non-human
primates by using an epitope sequence-dependent (ESD) mechanism. This
peptide exhibited a high level of serological reactivity (64%), which
resulted from the additive responses of two tandem epitopes (S<sub>597–603</sub> and S<sub>604–625</sub>) and a long-term
human B-cell memory response with antisera from convalescent SARS
patients. Thus, peptide-based vaccines against SARS-CoV could be engineered
to avoid ADE via elimination of the S<sub>597–603</sub> epitope.
We provide herein an alternative strategy to prepare a safe and effective
vaccine for ADE of viral infection by identifying and eliminating
epitope sequence-dependent enhancement of viral infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author><author><name sortKey="Peiris, M" uniqKey="Peiris M">M. Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Gunther, S" uniqKey="Gunther S">S. Günther</name></author><author><name sortKey="Preiser, W" uniqKey="Preiser W">W. Preiser</name></author><author><name sortKey="Van Der Werf, S" uniqKey="Van Der Werf S">S. van der Werf</name></author><author><name sortKey="Brodt, H R" uniqKey="Brodt H">H. R. Brodt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Shi, Z" uniqKey="Shi Z">Z. 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Mattsson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Japon</li><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Qidi" sort="Wang, Qidi" uniqKey="Wang Q" first="Qidi" last="Wang">Qidi Wang</name></noRegion><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name><name sortKey="Li, Taisheng" sort="Li, Taisheng" uniqKey="Li T" first="Taisheng" last="Li">Taisheng Li</name><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name><name sortKey="Liu, Jiangning" sort="Liu, Jiangning" uniqKey="Liu J" first="Jiangning" last="Liu">Jiangning Liu</name><name sortKey="Liu, Zijie" sort="Liu, Zijie" uniqKey="Liu Z" first="Zijie" last="Liu">Zijie Liu</name><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><name sortKey="Xie, Jing" sort="Xie, Jing" uniqKey="Xie J" first="Jing" last="Xie">Jing Xie</name><name sortKey="Xu, Yanfeng" sort="Xu, Yanfeng" uniqKey="Xu Y" first="Yanfeng" last="Xu">Yanfeng Xu</name><name sortKey="Zhang, Lianfeng" sort="Zhang, Lianfeng" uniqKey="Zhang L" first="Lianfeng" last="Zhang">Lianfeng Zhang</name><name sortKey="Zhu, Hua" sort="Zhu, Hua" uniqKey="Zhu H" first="Hua" last="Zhu">Hua Zhu</name></country><country name="Japon"><noRegion><name sortKey="Kuwahara, Kazuhiko" sort="Kuwahara, Kazuhiko" uniqKey="Kuwahara K" first="Kazuhiko" last="Kuwahara">Kazuhiko Kuwahara</name></noRegion><name sortKey="Morioka, Hiroshi" sort="Morioka, Hiroshi" uniqKey="Morioka H" first="Hiroshi" last="Morioka">Hiroshi Morioka</name><name sortKey="Sakaguchi, Nobuo" sort="Sakaguchi, Nobuo" uniqKey="Sakaguchi N" first="Nobuo" last="Sakaguchi">Nobuo Sakaguchi</name><name sortKey="Sakaguchi, Nobuo" sort="Sakaguchi, Nobuo" uniqKey="Sakaguchi N" first="Nobuo" last="Sakaguchi">Nobuo Sakaguchi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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