About: Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway

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About: Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway
Creator	Sui, Jianhua Jing, Huaiqi Kan, Biao Yan, Meiying Aird, Daniel Murakami, Akikazu Yammanuru, Anuradha Tamin, Azaibi Liu, Xin Xu, Jianguo Zhu, Quan Anderson, Larry Adams, Gregory Bellini, William Marasco, Wayne Yuan, Qing-An
topic	covid:ee0d298d09635c5ae72d4584fba105a705d25afb#this
Source	Medline; PMC
abstract	Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID) “hot spot” in a light chain CDR (complementarity determining region) alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM) of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural information in combination of chain-shuffling as well as hot-spot CDR mutagenesis, can be exploited to broaden neutralization activity, to improve anti-viral nAb therapies, and directly manipulate virus evolution.
has issue date	2008-11-07(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1000197
bibo:pmid	18989460
has license	cc0
sha1sum (hex)	ee0d298d09635c5ae72d4584fba105a705d25afb
schema:url	https://doi.org/10.1371/journal.ppat.1000197
resource representing a document's title	Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway
has PubMed Central identifier	PMC2572002
has PubMed identifier	18989460
schema:publication	PLoS Pathog
resource representing a document's body	covid:ee0d298d09635c5ae72d4584fba105a705d25afb#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/ee0d298d09635c5ae72d4584fba105a705d25afb
is schema:about of	named entity 'SARS-CoV' named entity 'successful' named entity 'combination' named entity 'Citation' named entity 'nAb' named entity 'recapitulated' named entity 'nAb' named entity 'exist' named entity 'animal' named entity 'Murakami' named entity 'sera' named entity 'virus evolution' named entity 'improve' named entity 'Pathway' named entity 'Neutralization' named entity 'Evolution' named entity 'DOMINANT' named entity 'PATHWAY' covid:arg/ee0d298d09635c5ae72d4584fba105a705d25afb named entity 'CORONAVIRUS' named entity 'PROTEIN ' named entity 'PRESENT' named entity 'PATHWAY' named entity 'STRUCTURAL' named entity 'VIRUS' named entity 'MARKEDLY' named entity 'FOUND' named entity 'CROSS' named entity 'NEUTRALIZING ANTIBODIES' named entity 'CORONAVIRUSES' named entity 'NAB' named entity 'FORCE' named entity 'FOCUSING' named entity 'DETAILED' named entity 'DIRECTLY' named entity 'SUCCESSFUL' named entity 'INTRODUCED' named entity 'COVS' named entity 'HUMAN' named entity 'PROVIDED' named entity 'DRIVING' named entity 'NATURAL INFECTION' named entity 'REPERTOIRE' named entity 'SOMATIC HYPERMUTATION' named entity 'EXAMINATION' named entity 'CDR' named entity 'PATHWAYS' named entity 'SUPPORT' named entity 'ANIMAL' named entity 'ESCAPE' named entity 'VIRUSES' named entity 'EPITOPE' named entity 'SERA' named entity 'SPIKE PROTEIN' named entity 'REGION' named entity 'STUDIES' named entity 'CITATION' named entity 'STRAIN' named entity 'SARS-COV' named entity 'RESPONSES' named entity 'RESULTS' named entity 'DOMINANT' named entity 'MUTAGENESIS' named entity 'HOT'

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