About: Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants

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About: Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants
Creator	Preiser, Wolfgang Poon, Leo Goudsmit, Jaap Cox, Freek Bakker, Arjen Chow, Vincent Doerr, Hans Peiris, Joseph Cheung, Chung Leung, Cynthia Bogaards, Johannes De Kruif, John Marissen, Wilfred Ter Meulen, Jan Van Den Brink, Edward Van Deventer, Els
source	Medline; PMC
abstract	BACKGROUND: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. CONCLUSIONS: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection.
has issue date	2006-07-04(xsd:dateTime)
bibo:doi	10.1371/journal.pmed.0030237
bibo:pmid	16796401
has license	cc-by
sha1sum (hex)	3650b941642ddc9c3627fdb8d415f8c8b69a4158
schema:url	https://doi.org/10.1371/journal.pmed.0030237
resource representing a document's title	Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants
has PubMed Central identifier	PMC1483912
has PubMed identifier	16796401
schema:publication	PLoS Med
resource representing a document's body	covid:3650b941642ddc9c3627fdb8d415f8c8b69a4158#body_text
is schema:about of	named entity 'MUTANTS' named entity 'COMBINATION' named entity 'COVERAGE' named entity 'MONOCLONAL ANTIBODY' named entity 'ESCAPE' named entity 'SARS CORONAVIRUS' named entity 'SYNERGY' named entity 'HUMAN' named entity 'Human' named entity 'Combination' named entity 'Coronavirus' named entity 'Human Monoclonal Antibody' named entity 'virus' named entity 'abortive infection' named entity 'antibody-dependent enhancement' named entity 'mAbs' named entity 'light chains' named entity 'Biacore' named entity 'RBD' named entity 'SARS-CoV' named entity 'mice' named entity 'antibody' named entity 'wild-type' named entity 'viral replication' named entity 'agarose' named entity 'immortalization' named entity 'SARS-CoV' named entity 'SARS' named entity 'SARS' named entity 'viruses' named entity 'Biacore' named entity 'mutation' named entity 'antibodies' named entity 'SARS-CoV' named entity 'viruses' named entity 'wild-type' named entity 'serially diluted' named entity 'virus' named entity 'culling' named entity 'Biacore' named entity 'SARS-CoV' named entity 'potency' named entity 'Virginia' named entity 'mAbs' named entity 'SARS' named entity 'macrophages' named entity 'antibodies' named entity 'serum' named entity 'virus' named entity 'SARS-CoV' named entity 'virus' named entity 'selective pressure' named entity 'streptavidin' named entity 'SARS-CoV' named entity 'homologous' named entity 'epitopes' named entity 'SARS-CoV' named entity 'SARS-CoV' named entity 'potencies' named entity 'mAb' named entity 'antibodies' named entity 'mRNA' named entity 'B-cells' named entity 'SARS' named entity 'epitopes' named entity 'virus'

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