Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge
Identifieur interne : 000299 ( PascalFrancis/Corpus ); précédent : 000298; suivant : 000300Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge
Auteurs : Barry Rockx ; Davide Corti ; Eric Donaldson ; Timothy Sheahan ; Konrad Stadler ; Antonio Lanzavecchia ; Ralph BaricSource :
- Journal of virology [ 0022-538X ] ; 2008.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants.
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Format Inist (serveur)
NO : | PASCAL 08-0181246 INIST |
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ET : | Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge |
AU : | ROCKX (Barry); CORTI (Davide); DONALDSON (Eric); SHEAHAN (Timothy); STADLER (Konrad); LANZAVECCHIA (Antonio); BARIC (Ralph) |
AF : | Department of Epidemiology, University of North Carolina/Chapel Hill, North Carolina/Etats-Unis (1 aut., 7 aut.); Institute for Research in Biomedicine/Bellinzona/Suisse (2 aut., 6 aut.); Department of Microbiology and Immunology, University of North Carolina/Chapel Hill, North Carolina/Etats-Unis (3 aut., 4 aut., 7 aut.); Novartis Vaccines, Via Fiorentina 1/53100 Siena/Italie (5 aut.) |
DT : | Publication en série; Niveau analytique |
SO : | Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2008; Vol. 82; No. 7; Pp. 3220-3235; Bibl. 57 ref. |
LA : | Anglais |
EA : | Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants. |
CC : | 002A05C10; 002A05C07 |
FD : | Homme; Coronavirus; Protection croisée; Anticorps neutralisant; Anticorps monoclonal; Aigu; Virologie |
FG : | Coronaviridae; Nidovirales; Virus |
ED : | Human; Coronavirus; Cross protection; Neutralizing antibody; Monoclonal antibody; Acute; Virology |
EG : | Coronaviridae; Nidovirales; Virus |
SD : | Hombre; Coronavirus; Protección cruzada; anticuerpo neutralizante; Anticuerpo monoclonal; Agudo; Virología |
LO : | INIST-13592.354000183723680050 |
ID : | 08-0181246 |
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Pascal:08-0181246Le document en format XML
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<front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants.</div>
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<ET>Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge</ET>
<AU>ROCKX (Barry); CORTI (Davide); DONALDSON (Eric); SHEAHAN (Timothy); STADLER (Konrad); LANZAVECCHIA (Antonio); BARIC (Ralph)</AU>
<AF>Department of Epidemiology, University of North Carolina/Chapel Hill, North Carolina/Etats-Unis (1 aut., 7 aut.); Institute for Research in Biomedicine/Bellinzona/Suisse (2 aut., 6 aut.); Department of Microbiology and Immunology, University of North Carolina/Chapel Hill, North Carolina/Etats-Unis (3 aut., 4 aut., 7 aut.); Novartis Vaccines, Via Fiorentina 1/53100 Siena/Italie (5 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2008; Vol. 82; No. 7; Pp. 3220-3235; Bibl. 57 ref.</SO>
<LA>Anglais</LA>
<EA>Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants.</EA>
<CC>002A05C10; 002A05C07</CC>
<FD>Homme; Coronavirus; Protection croisée; Anticorps neutralisant; Anticorps monoclonal; Aigu; Virologie</FD>
<FG>Coronaviridae; Nidovirales; Virus</FG>
<ED>Human; Coronavirus; Cross protection; Neutralizing antibody; Monoclonal antibody; Acute; Virology</ED>
<EG>Coronaviridae; Nidovirales; Virus</EG>
<SD>Hombre; Coronavirus; Protección cruzada; anticuerpo neutralizante; Anticuerpo monoclonal; Agudo; Virología</SD>
<LO>INIST-13592.354000183723680050</LO>
<ID>08-0181246</ID>
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