A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge
Identifieur interne : 002391 ( Main/Exploration ); précédent : 002390; suivant : 002392A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge
Auteurs : Meagan Bolles [États-Unis] ; Damon Deming [États-Unis] ; Kristin Long [États-Unis] ; Sudhakar Agnihothram [États-Unis] ; Alan Whitmore [États-Unis] ; Martin Ferris [États-Unis] ; William Funkhouser [États-Unis] ; Lisa Gralinski [États-Unis] ; Allison Totura [États-Unis] ; Mark Heise [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2011.
Descripteurs français
- KwdFr :
- ARN messager (génétique), Animaux, Anticorps antiviraux (immunologie), Cellules Vero, Femelle, Poumon (anatomopathologie), Poumon (immunologie), Poumon (virologie), Poumon éosinophile (anatomopathologie), Poumon éosinophile (immunologie), Poumon éosinophile (virologie), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), Réaction de polymérisation en chaine en temps réel, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Technique de Western, Test ELISA, Tests de neutralisation, Vaccination, Vaccins antiviraux (usage thérapeutique), Vaccins inactivés (usage thérapeutique), Virus du SRAS (génétique), Virus du SRAS (immunologie).
- MESH :
- anatomopathologie : Poumon, Poumon éosinophile.
- génétique : ARN messager, Protéines de l'enveloppe virale, Virus du SRAS.
- immunologie : Anticorps antiviraux, Poumon, Poumon éosinophile, Syndrome respiratoire aigu sévère, Virus du SRAS.
- métabolisme : Protéines de l'enveloppe virale.
- usage thérapeutique : Vaccins antiviraux, Vaccins inactivés.
- virologie : Poumon, Poumon éosinophile, Syndrome respiratoire aigu sévère.
- Pascal (Inist)
- Wicri :
- topic : Vaccin.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (immunology), Blotting, Western, Chlorocebus aethiops, Coronavirus, Enzyme-Linked Immunosorbent Assay, Female, Lung (immunology), Lung (pathology), Lung (virology), Mice, Mice, Inbred BALB C, Mouse, Neutralization Tests, Pulmonary Eosinophilia (immunology), Pulmonary Eosinophilia (pathology), Pulmonary Eosinophilia (virology), RNA, Messenger (genetics), Real-Time Polymerase Chain Reaction, SARS Virus (genetics), SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (prevention & control), Severe Acute Respiratory Syndrome (virology), Severe acute respiratory syndrome, Vaccination, Vaccine, Vaccines, Inactivated (therapeutic use), Vero Cells, Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism), Viral Vaccines (therapeutic use).
- MESH :
- chemical , genetics : RNA, Messenger, Viral Envelope Proteins.
- chemical , immunology : Antibodies, Viral.
- genetics : SARS Virus.
- immunology : Lung, Pulmonary Eosinophilia, SARS Virus, Severe Acute Respiratory Syndrome.
- chemical , metabolism : Viral Envelope Proteins.
- pathology : Lung, Pulmonary Eosinophilia.
- prevention & control : Severe Acute Respiratory Syndrome.
- chemical , therapeutic use : Vaccines, Inactivated, Viral Vaccines.
- virology : Lung, Pulmonary Eosinophilia, Severe Acute Respiratory Syndrome.
- Animals, Blotting, Western, Chlorocebus aethiops, Enzyme-Linked Immunosorbent Assay, Female, Mice, Mice, Inbred BALB C, Neutralization Tests, Real-Time Polymerase Chain Reaction, Vaccination, Vero Cells.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.
Url:
Affiliations:
- États-Unis
- Caroline du Nord
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
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Le document en format XML
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Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Deming, Damon" sort="Deming, Damon" uniqKey="Deming D" first="Damon" last="Deming">Damon Deming</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Long, Kristin" sort="Long, Kristin" uniqKey="Long K" first="Kristin" last="Long">Kristin Long</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Whitmore, Alan" sort="Whitmore, Alan" uniqKey="Whitmore A" first="Alan" last="Whitmore">Alan Whitmore</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Ferris, Martin" sort="Ferris, Martin" uniqKey="Ferris M" first="Martin" last="Ferris">Martin Ferris</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Funkhouser, William" sort="Funkhouser, William" uniqKey="Funkhouser W" first="William" last="Funkhouser">William Funkhouser</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Pathology, University of North Carolina School of Medicine</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Gralinski, Lisa" sort="Gralinski, Lisa" uniqKey="Gralinski L" first="Lisa" last="Gralinski">Lisa Gralinski</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Totura, Allison" sort="Totura, Allison" uniqKey="Totura A" first="Allison" last="Totura">Allison Totura</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author><author><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Department of Genetics, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></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="4"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region><settlement type="city">Chapel Hill (Caroline du Nord)</settlement></placeName><orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Viral (immunology)</term><term>Blotting, Western</term><term>Chlorocebus aethiops</term><term>Coronavirus</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Lung (immunology)</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mouse</term><term>Neutralization Tests</term><term>Pulmonary Eosinophilia (immunology)</term><term>Pulmonary Eosinophilia (pathology)</term><term>Pulmonary Eosinophilia (virology)</term><term>RNA, Messenger (genetics)</term><term>Real-Time Polymerase Chain Reaction</term><term>SARS Virus (genetics)</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>Severe acute respiratory syndrome</term><term>Vaccination</term><term>Vaccine</term><term>Vaccines, Inactivated (therapeutic use)</term><term>Vero Cells</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (metabolism)</term><term>Viral Vaccines (therapeutic use)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Cellules Vero</term><term>Femelle</term><term>Poumon (anatomopathologie)</term><term>Poumon (immunologie)</term><term>Poumon (virologie)</term><term>Poumon éosinophile (anatomopathologie)</term><term>Poumon éosinophile (immunologie)</term><term>Poumon éosinophile (virologie)</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Syndrome respiratoire aigu sévère ()</term><term>Syndrome respiratoire aigu sévère (immunologie)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Technique de Western</term><term>Test ELISA</term><term>Tests de neutralisation</term><term>Vaccination</term><term>Vaccins antiviraux (usage thérapeutique)</term><term>Vaccins inactivés (usage thérapeutique)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Messenger</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term><term>Poumon éosinophile</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>Protéines de l'enveloppe virale</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Poumon</term><term>Poumon éosinophile</term><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Lung</term><term>Pulmonary Eosinophilia</term><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term><term>Pulmonary Eosinophilia</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Vaccines, Inactivated</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Vaccins antiviraux</term><term>Vaccins inactivés</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Poumon</term><term>Poumon éosinophile</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term><term>Pulmonary Eosinophilia</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blotting, Western</term><term>Chlorocebus aethiops</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Neutralization Tests</term><term>Real-Time Polymerase Chain Reaction</term><term>Vaccination</term><term>Vero Cells</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Coronavirus</term><term>Femelle</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Syndrome respiratoire aigu sévère</term><term>Technique de Western</term><term>Test ELISA</term><term>Tests de neutralisation</term><term>Vaccin</term><term>Syndrome respiratoire aigu sévère</term><term>Vaccination</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccin</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li></region><settlement><li>Chapel Hill (Caroline du Nord)</li></settlement><orgName><li>Université de Caroline du Nord à Chapel Hill</li></orgName></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Bolles, Meagan" sort="Bolles, Meagan" uniqKey="Bolles M" first="Meagan" last="Bolles">Meagan Bolles</name></region><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Deming, Damon" sort="Deming, Damon" uniqKey="Deming D" first="Damon" last="Deming">Damon Deming</name><name sortKey="Ferris, Martin" sort="Ferris, Martin" uniqKey="Ferris M" first="Martin" last="Ferris">Martin Ferris</name><name sortKey="Funkhouser, William" sort="Funkhouser, William" uniqKey="Funkhouser W" first="William" last="Funkhouser">William Funkhouser</name><name sortKey="Gralinski, Lisa" sort="Gralinski, Lisa" uniqKey="Gralinski L" first="Lisa" last="Gralinski">Lisa Gralinski</name><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><name sortKey="Long, Kristin" sort="Long, Kristin" uniqKey="Long K" first="Kristin" last="Long">Kristin Long</name><name sortKey="Totura, Allison" sort="Totura, Allison" uniqKey="Totura A" first="Allison" last="Totura">Allison Totura</name><name sortKey="Whitmore, Alan" sort="Whitmore, Alan" uniqKey="Whitmore A" first="Alan" last="Whitmore">Alan Whitmore</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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