In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2022-9-22), p. e0274283-
Abstract:
In recent years, new direct-acting antivirals for hepatitis C virus (HCV) have been approved, but hepatitis C continues to pose a threat to human health. It is important to develop neutralizing anti-HCV antibodies to prevent medical and accidental infection, such as might occur via liver transplantation of chronic HCV patients and needle-stick accidents in the clinic. In this study, we sought to obtain anti-HCV antibodies using phage display screening. Phages displaying human hepatocellular carcinoma patient-derived antibodies were screened by 4 rounds of biopanning with genotype-1b and -2a HCV envelope E2 protein adsorbed to magnetic beads. The three antibodies obtained from this screen had reactivity against E2 proteins derived from both genotype-1b and -2a strains. However, in epitope analysis, these antibodies did not recognize linear peptides from an overlapping E2 epitope peptide library, and did not bind to denatured E2 protein. In addition, these antibodies showed cross-genotypic neutralizing activity against genotype-1a, -1b, -2a, and -3a cell culture-generated infectious HCV particles (HCVcc). Moreover, emergence of viral escape mutants was not observed after repeated rounds of passaging of HCV-infected cells in the presence of one such antibody, e2d066. Furthermore, injection of the e2d066 antibody into human hepatocyte-transplanted immunodeficient mice inhibited infection by J6/JFH-1 HCVcc. In conclusion, we identified conformational epitope-recognizing, cross-genotypic neutralizing antibodies using phage display screening. Notably, e2d066 antibody did not select for escape mutant emergence in vitro and demonstrated neutralizing activity in vivo. Our results suggested that these antibodies may serve as prophylactic and therapeutic agents.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0274283
DOI:
10.1371/journal.pone.0274283.g001
DOI:
10.1371/journal.pone.0274283.g002
DOI:
10.1371/journal.pone.0274283.g003
DOI:
10.1371/journal.pone.0274283.g004
DOI:
10.1371/journal.pone.0274283.g005
DOI:
10.1371/journal.pone.0274283.t001
DOI:
10.1371/journal.pone.0274283.t002
DOI:
10.1371/journal.pone.0274283.t003
DOI:
10.1371/journal.pone.0274283.t004
DOI:
10.1371/journal.pone.0274283.s001
DOI:
10.1371/journal.pone.0274283.s002
DOI:
10.1371/journal.pone.0274283.s003
DOI:
10.1371/journal.pone.0274283.s004
DOI:
10.1371/journal.pone.0274283.s005
DOI:
10.1371/journal.pone.0274283.s006
DOI:
10.1371/journal.pone.0274283.s007
DOI:
10.1371/journal.pone.0274283.s008
DOI:
10.1371/journal.pone.0274283.s009
DOI:
10.1371/journal.pone.0274283.s010
DOI:
10.1371/journal.pone.0274283.s011
DOI:
10.1371/journal.pone.0274283.s012
DOI:
10.1371/journal.pone.0274283.r001
DOI:
10.1371/journal.pone.0274283.r002
DOI:
10.1371/journal.pone.0274283.r003
DOI:
10.1371/journal.pone.0274283.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
Bookmarklink