Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus.
Identifieur interne : 001613 ( Main/Exploration ); précédent : 001612; suivant : 001614Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus.
Auteurs : Davide Corti [Suisse] ; Jincun Zhao [République populaire de Chine] ; Mattia Pedotti [Suisse] ; Luca Simonelli [Suisse] ; Sudhakar Agnihothram [États-Unis] ; Craig Fett [États-Unis] ; Blanca Fernandez-Rodriguez [Suisse] ; Mathilde Foglierini [Suisse] ; Gloria Agatic [Suisse] ; Fabrizia Vanzetta [Suisse] ; Robin Gopal [Royaume-Uni] ; Christopher J. Langrish [Royaume-Uni] ; Nicholas A. Barrett [Royaume-Uni] ; Federica Sallusto [Suisse] ; Ralph S. Baric [États-Unis] ; Luca Varani [Suisse] ; Maria Zambon [Royaume-Uni] ; Stanley Perlman [États-Unis] ; Antonio Lanzavecchia [Suisse]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2015.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Animaux, Anticorps antiviraux (immunologie), Anticorps monoclonaux (immunologie), Anticorps neutralisants (immunologie), Cellules CHO, Conformation moléculaire, Coronavirus du syndrome respiratoire du Moyen-Orient (), Cricetinae, Cricetulus, Dipeptidyl peptidase 4 (), Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus (), Humains, Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Liaison aux protéines, Lymphocytes B (immunologie), Mutation, Mâle, Mémoire immunologique, Similitude de séquences d'acides aminés, Sites de fixation, Souris, Souris de lignée BALB C, Séquence d'acides aminés, Test ELISA, Vaccins antiviraux.
- MESH :
- immunologie : Anticorps antiviraux, Anticorps monoclonaux, Anticorps neutralisants, Infections à coronavirus, Lymphocytes B.
- virologie : Infections à coronavirus.
- Adulte d'âge moyen, Animaux, Cellules CHO, Conformation moléculaire, Coronavirus du syndrome respiratoire du Moyen-Orient, Cricetinae, Cricetulus, Dipeptidyl peptidase 4, Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Humains, Liaison aux protéines, Mutation, Mâle, Mémoire immunologique, Similitude de séquences d'acides aminés, Sites de fixation, Souris, Souris de lignée BALB C, Séquence d'acides aminés, Test ELISA, Vaccins antiviraux.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Monoclonal (immunology), Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), B-Lymphocytes (immunology), Binding Sites, CHO Cells, Coronavirus Infections (immunology), Coronavirus Infections (virology), Cricetinae, Cricetulus, Dipeptidyl Peptidase 4 (chemistry), Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunologic Memory, Male, Mice, Mice, Inbred BALB C, Middle Aged, Middle East Respiratory Syndrome Coronavirus (drug effects), Molecular Conformation, Molecular Sequence Data, Mutation, Protein Binding, Sequence Homology, Amino Acid, Spike Glycoprotein, Coronavirus (chemistry), Viral Vaccines.
- MESH :
- chemical , chemistry : Dipeptidyl Peptidase 4, Spike Glycoprotein, Coronavirus.
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral.
- drug effects : Middle East Respiratory Syndrome Coronavirus.
- immunology : B-Lymphocytes, Coronavirus Infections.
- virology : Coronavirus Infections.
- Amino Acid Sequence, Animals, Binding Sites, CHO Cells, Cricetinae, Cricetulus, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunologic Memory, Male, Mice, Mice, Inbred BALB C, Middle Aged, Molecular Conformation, Molecular Sequence Data, Mutation, Protein Binding, Sequence Homology, Amino Acid, Viral Vaccines.
Abstract
Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV-neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses.
DOI: 10.1073/pnas.1510199112
PubMed: 26216974
Affiliations:
- Royaume-Uni, République populaire de Chine, Suisse, États-Unis
- Caroline du Nord, Guangdong, Iowa
- Iowa City, Jiangmen
- Université de l'Iowa
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Le document en format XML
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sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology, University of Iowa, Iowa City, IA 52240; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, University of Iowa, Iowa City, IA 52240; State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName><orgName type="university">Université de l'Iowa</orgName><placeName><settlement type="city">Iowa City</settlement><region type="state">Iowa</region></placeName></affiliation></author><author><name sortKey="Pedotti, Mattia" sort="Pedotti, Mattia" uniqKey="Pedotti M" first="Mattia" last="Pedotti">Mattia Pedotti</name><affiliation wicri:level="1"><nlm:affiliation>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona</wicri:regionArea><wicri:noRegion>6500 Bellinzona</wicri:noRegion></affiliation></author><author><name sortKey="Simonelli, Luca" sort="Simonelli, Luca" uniqKey="Simonelli L" first="Luca" last="Simonelli">Luca Simonelli</name><affiliation wicri:level="1"><nlm:affiliation>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona</wicri:regionArea><wicri:noRegion>6500 Bellinzona</wicri:noRegion></affiliation></author><author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Fernandez Rodriguez, Blanca" sort="Fernandez Rodriguez, Blanca" uniqKey="Fernandez Rodriguez B" first="Blanca" last="Fernandez-Rodriguez">Blanca Fernandez-Rodriguez</name><affiliation wicri:level="1"><nlm:affiliation>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona</wicri:regionArea><wicri:noRegion>6500 Bellinzona</wicri:noRegion></affiliation></author><author><name sortKey="Foglierini, Mathilde" sort="Foglierini, Mathilde" uniqKey="Foglierini M" first="Mathilde" last="Foglierini">Mathilde Foglierini</name><affiliation wicri:level="1"><nlm:affiliation>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona</wicri:regionArea><wicri:noRegion>6500 Bellinzona</wicri:noRegion></affiliation></author><author><name sortKey="Agatic, Gloria" sort="Agatic, Gloria" uniqKey="Agatic G" first="Gloria" last="Agatic">Gloria Agatic</name><affiliation wicri:level="1"><nlm:affiliation>Humabs BioMed SA, 6500 Bellinzona, Switzerland;</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Humabs BioMed SA, 6500 Bellinzona</wicri:regionArea><wicri:noRegion>6500 Bellinzona</wicri:noRegion></affiliation></author><author><name sortKey="Vanzetta, Fabrizia" sort="Vanzetta, Fabrizia" uniqKey="Vanzetta F" first="Fabrizia" last="Vanzetta">Fabrizia Vanzetta</name><affiliation wicri:level="1"><nlm:affiliation>Humabs BioMed SA, 6500 Bellinzona, Switzerland;</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Humabs BioMed SA, 6500 Bellinzona</wicri:regionArea><wicri:noRegion>6500 Bellinzona</wicri:noRegion></affiliation></author><author><name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name><affiliation wicri:level="1"><nlm:affiliation>Microbiology Services Colindale, Public Health England, London NW9 5HT, United Kingdom;</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Microbiology Services Colindale, Public Health England, London NW9 5HT</wicri:regionArea><wicri:noRegion>London NW9 5HT</wicri:noRegion></affiliation></author><author><name sortKey="Langrish, Christopher J" sort="Langrish, Christopher J" uniqKey="Langrish C" first="Christopher J" last="Langrish">Christopher J. Langrish</name><affiliation wicri:level="1"><nlm:affiliation>Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH, United Kingdom;</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH</wicri:regionArea><wicri:noRegion>London SE1 7EH</wicri:noRegion></affiliation></author><author><name sortKey="Barrett, Nicholas A" sort="Barrett, Nicholas A" uniqKey="Barrett N" first="Nicholas A" last="Barrett">Nicholas A. Barrett</name><affiliation wicri:level="1"><nlm:affiliation>Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH, United Kingdom; King's College London, Strand, London WC2R 2LS, United Kingdom;</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Guy's and St. Thomas' National Health Service Foundation Trust, London SE1 7EH, United Kingdom; King's College London, Strand, London WC2R 2LS</wicri:regionArea><wicri:noRegion>London WC2R 2LS</wicri:noRegion></affiliation></author><author><name sortKey="Sallusto, Federica" sort="Sallusto, Federica" uniqKey="Sallusto F" first="Federica" last="Sallusto">Federica Sallusto</name><affiliation wicri:level="1"><nlm:affiliation>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona</wicri:regionArea><wicri:noRegion>6500 Bellinzona</wicri:noRegion></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Varani, Luca" sort="Varani, Luca" uniqKey="Varani L" first="Luca" last="Varani">Luca Varani</name><affiliation wicri:level="1"><nlm:affiliation>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland;</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona</wicri:regionArea><wicri:noRegion>6500 Bellinzona</wicri:noRegion></affiliation></author><author><name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name><affiliation wicri:level="1"><nlm:affiliation>Microbiology Services Colindale, Public Health England, London NW9 5HT, United Kingdom;</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Microbiology Services Colindale, Public Health England, London NW9 5HT</wicri:regionArea><wicri:noRegion>London NW9 5HT</wicri:noRegion></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, University of Iowa, Iowa City, IA 52240;</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Microbiology, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name><affiliation wicri:level="1"><nlm:affiliation>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Institute of Microbiology, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, Switzerland lanzavecchia@irb.usi.ch.</nlm:affiliation><country wicri:rule="url">Suisse</country><wicri:regionArea>Immune Regulation Unit, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Institute of Microbiology, Eidgenössische Technische Hochschule Zurich, 8093 Zurich</wicri:regionArea><wicri:noRegion>8093 Zurich</wicri:noRegion></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antibodies, Monoclonal (immunology)</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Viral (immunology)</term><term>B-Lymphocytes (immunology)</term><term>Binding Sites</term><term>CHO Cells</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (virology)</term><term>Cricetinae</term><term>Cricetulus</term><term>Dipeptidyl Peptidase 4 (chemistry)</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Humans</term><term>Immunologic Memory</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Middle Aged</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Molecular Conformation</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Protein Binding</term><term>Sequence Homology, Amino Acid</term><term>Spike Glycoprotein, Coronavirus (chemistry)</term><term>Viral Vaccines</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps monoclonaux (immunologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Cellules CHO</term><term>Conformation moléculaire</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Cricetinae</term><term>Cricetulus</term><term>Dipeptidyl peptidase 4 ()</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus ()</term><term>Humains</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (virologie)</term><term>Liaison aux protéines</term><term>Lymphocytes B (immunologie)</term><term>Mutation</term><term>Mâle</term><term>Mémoire immunologique</term><term>Similitude de séquences d'acides aminés</term><term>Sites de fixation</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Séquence d'acides aminés</term><term>Test ELISA</term><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term><term>Anticorps neutralisants</term><term>Infections à coronavirus</term><term>Lymphocytes B</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>B-Lymphocytes</term><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Binding Sites</term><term>CHO Cells</term><term>Cricetinae</term><term>Cricetulus</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Humans</term><term>Immunologic Memory</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Middle Aged</term><term>Molecular Conformation</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Protein Binding</term><term>Sequence Homology, Amino Acid</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Animaux</term><term>Cellules CHO</term><term>Conformation moléculaire</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Cricetinae</term><term>Cricetulus</term><term>Dipeptidyl peptidase 4</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Liaison aux protéines</term><term>Mutation</term><term>Mâle</term><term>Mémoire immunologique</term><term>Similitude de séquences d'acides aminés</term><term>Sites de fixation</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Séquence d'acides aminés</term><term>Test ELISA</term><term>Vaccins antiviraux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a previously unidentified coronavirus (CoV), likely transmitted to humans by infected camels. There is no licensed vaccine or antiviral for MERS, therefore new prophylactic and therapeutic strategies to combat human infections are needed. In this study, we describe, for the first time, to our knowledge, the isolation of a potent MERS-CoV-neutralizing antibody from memory B cells of an infected individual. The antibody, named LCA60, binds to a novel site on the spike protein and potently neutralizes infection of multiple MERS-CoV isolates by interfering with the binding to the cellular receptor CD26. Importantly, using mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV, we show that LCA60 can effectively protect in both prophylactic and postexposure settings. This antibody can be used for prophylaxis, for postexposure prophylaxis of individuals at risk, or for the treatment of human cases of MERS-CoV infection. The fact that it took only 4 mo from the initial screening of B cells derived from a convalescent patient for the development of a stable chinese hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5 g/L provides an example of a rapid pathway toward the generation of effective antiviral therapies against emerging viruses. </div></front></TEI><affiliations><list><country><li>Royaume-Uni</li><li>République populaire de Chine</li><li>Suisse</li><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Guangdong</li><li>Iowa</li></region><settlement><li>Iowa City</li><li>Jiangmen</li></settlement><orgName><li>Université de l'Iowa</li></orgName></list><tree><country name="Suisse"><noRegion><name sortKey="Corti, Davide" sort="Corti, Davide" uniqKey="Corti D" first="Davide" last="Corti">Davide Corti</name></noRegion><name sortKey="Agatic, Gloria" sort="Agatic, Gloria" uniqKey="Agatic G" first="Gloria" last="Agatic">Gloria Agatic</name><name sortKey="Fernandez Rodriguez, Blanca" sort="Fernandez Rodriguez, Blanca" uniqKey="Fernandez Rodriguez B" first="Blanca" last="Fernandez-Rodriguez">Blanca Fernandez-Rodriguez</name><name sortKey="Foglierini, Mathilde" sort="Foglierini, Mathilde" uniqKey="Foglierini M" first="Mathilde" last="Foglierini">Mathilde Foglierini</name><name sortKey="Lanzavecchia, Antonio" sort="Lanzavecchia, Antonio" uniqKey="Lanzavecchia A" first="Antonio" last="Lanzavecchia">Antonio Lanzavecchia</name><name sortKey="Pedotti, Mattia" sort="Pedotti, Mattia" uniqKey="Pedotti M" first="Mattia" last="Pedotti">Mattia Pedotti</name><name sortKey="Sallusto, Federica" sort="Sallusto, Federica" uniqKey="Sallusto F" first="Federica" last="Sallusto">Federica Sallusto</name><name sortKey="Simonelli, Luca" sort="Simonelli, Luca" uniqKey="Simonelli L" first="Luca" last="Simonelli">Luca Simonelli</name><name sortKey="Vanzetta, Fabrizia" sort="Vanzetta, Fabrizia" uniqKey="Vanzetta F" first="Fabrizia" last="Vanzetta">Fabrizia Vanzetta</name><name sortKey="Varani, Luca" sort="Varani, Luca" uniqKey="Varani L" first="Luca" last="Varani">Luca Varani</name></country><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Zhao, Jincun" sort="Zhao, Jincun" uniqKey="Zhao J" first="Jincun" last="Zhao">Jincun Zhao</name></region></country><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name></region><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><name sortKey="Fett, Craig" sort="Fett, Craig" uniqKey="Fett C" first="Craig" last="Fett">Craig Fett</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name></noRegion><name sortKey="Barrett, Nicholas A" sort="Barrett, Nicholas A" uniqKey="Barrett N" first="Nicholas A" last="Barrett">Nicholas A. Barrett</name><name sortKey="Langrish, Christopher J" sort="Langrish, Christopher J" uniqKey="Langrish C" first="Christopher J" last="Langrish">Christopher J. Langrish</name><name sortKey="Zambon, Maria" sort="Zambon, Maria" uniqKey="Zambon M" first="Maria" last="Zambon">Maria Zambon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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