Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms.
Identifieur interne : 002B02 ( Main/Exploration ); précédent : 002B01; suivant : 002B03Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms.
Auteurs : Melissa M. Coughlin [États-Unis] ; John Babcook ; Bellur S. PrabhakarSource :
- Virology [ 1096-0341 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps antiviraux (pharmacologie), Anticorps monoclonaux (immunologie), Anticorps monoclonaux (pharmacologie), Antiviraux (pharmacologie), Attachement viral, Cellules Vero, Concentration inhibitrice 50, Humains, Mutation, Pénétration virale, Tests de neutralisation, Virus du SRAS (immunologie), Virus du SRAS (physiologie).
- MESH :
- immunologie : Anticorps antiviraux, Anticorps monoclonaux, Virus du SRAS.
- pharmacologie : Anticorps antiviraux, Anticorps monoclonaux, Antiviraux.
- physiologie : Virus du SRAS.
- Animaux, Attachement viral, Cellules Vero, Concentration inhibitrice 50, Humains, Mutation, Pénétration virale, Tests de neutralisation.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (immunology), Antibodies, Monoclonal (pharmacology), Antibodies, Viral (immunology), Antibodies, Viral (pharmacology), Antiviral Agents (pharmacology), Chlorocebus aethiops, Humans, Inhibitory Concentration 50, Mutation, Neutralization Tests, SARS Virus (immunology), SARS Virus (physiology), Vero Cells, Virus Attachment, Virus Internalization.
- MESH :
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Viral.
- chemical , pharmacology : Antibodies, Monoclonal, Antibodies, Viral, Antiviral Agents.
- immunology : SARS Virus.
- physiology : SARS Virus.
- Animals, Chlorocebus aethiops, Humans, Inhibitory Concentration 50, Mutation, Neutralization Tests, Vero Cells, Virus Attachment, Virus Internalization.
Abstract
SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing epitopes within the RBD inhibit infection by preventing viral attachment to the cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying ability of the mAbs to select escape mutants when used individually. However, a mixture of antibodies could effectively neutralize a range of mutant viruses. These data strongly suggest that a mixture containing antibodies recognizing distinct regions and targeting more than one step in viral entry is likely to be more effective in neutralizing the virus and suppressing the generation of escape mutants, and thus potentially constitute a highly effective passive immunotherapy.
DOI: 10.1016/j.virol.2009.07.028
PubMed: 19748648
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing epitopes within the RBD inhibit infection by preventing viral attachment to the cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying ability of the mAbs to select escape mutants when used individually. However, a mixture of antibodies could effectively neutralize a range of mutant viruses. These data strongly suggest that a mixture containing antibodies recognizing distinct regions and targeting more than one step in viral entry is likely to be more effective in neutralizing the virus and suppressing the generation of escape mutants, and thus potentially constitute a highly effective passive immunotherapy.</div>
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