In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 5 ( 2021-5-7), p. e3001209-
Abstract:
The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. From a large panel of isolated antibodies, 25 antibodies showed potent neutralizing activities at sub-nanomolar levels by engaging the spike receptor-binding domain (RBD). Importantly, one human NAb, termed PR1077, from the H2L2 platform and 2 humanized NAb, including PR953 and PR961, were further characterized and subjected for subsequent structural analysis. High-resolution X-ray crystallography structures unveiled novel epitopes on the receptor-binding motif (RBM) for PR1077 and PR953, which directly compete with human angiotensin-converting enzyme 2 (hACE2) for binding, and a novel non-blocking epitope on the neighboring site near RBM for PR961. Moreover, we further tested the antiviral efficiency of PR1077 in the Ad5-hACE2 transduction mouse model of COVID-19. A single injection provided potent protection against SARS-CoV-2 infection in either prophylactic or treatment groups. Taken together, these results shed light on the development of mAb-related therapeutic interventions for COVID-19.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001209
DOI:
10.1371/journal.pbio.3001209.g001
DOI:
10.1371/journal.pbio.3001209.g002
DOI:
10.1371/journal.pbio.3001209.g003
DOI:
10.1371/journal.pbio.3001209.g004
DOI:
10.1371/journal.pbio.3001209.g005
DOI:
10.1371/journal.pbio.3001209.s001
DOI:
10.1371/journal.pbio.3001209.s002
DOI:
10.1371/journal.pbio.3001209.s003
DOI:
10.1371/journal.pbio.3001209.s004
DOI:
10.1371/journal.pbio.3001209.s005
DOI:
10.1371/journal.pbio.3001209.s006
DOI:
10.1371/journal.pbio.3001209.s007
DOI:
10.1371/journal.pbio.3001209.s008
DOI:
10.1371/journal.pbio.3001209.s009
DOI:
10.1371/journal.pbio.3001209.s010
DOI:
10.1371/journal.pbio.3001209.s011
DOI:
10.1371/journal.pbio.3001209.s012
DOI:
10.1371/journal.pbio.3001209.s013
DOI:
10.1371/journal.pbio.3001209.s014
DOI:
10.1371/journal.pbio.3001209.s015
DOI:
10.1371/journal.pbio.3001209.s016
DOI:
10.1371/journal.pbio.3001209.s017
DOI:
10.1371/journal.pbio.3001209.s018
DOI:
10.1371/journal.pbio.3001209.s019
DOI:
10.1371/journal.pbio.3001209.s020
DOI:
10.1371/journal.pbio.3001209.s021
DOI:
10.1371/journal.pbio.3001209.s022
DOI:
10.1371/journal.pbio.3001209.s023
DOI:
10.1371/journal.pbio.3001209.s024
DOI:
10.1371/journal.pbio.3001209.s025
DOI:
10.1371/journal.pbio.3001209.s026
DOI:
10.1371/journal.pbio.3001209.s027
DOI:
10.1371/journal.pbio.3001209.s028
DOI:
10.1371/journal.pbio.3001209.s029
DOI:
10.1371/journal.pbio.3001209.s030
DOI:
10.1371/journal.pbio.3001209.r001
DOI:
10.1371/journal.pbio.3001209.r002
DOI:
10.1371/journal.pbio.3001209.r003
DOI:
10.1371/journal.pbio.3001209.r004
DOI:
10.1371/journal.pbio.3001209.r005
DOI:
10.1371/journal.pbio.3001209.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
Bookmarklink