An Antigenically Diverse, Representative Panel of Envelope Glycoproteins for Hepatitis C Virus Vaccine Development.
Antigenic Variation
/ genetics
Antigens, Viral
/ genetics
Broadly Neutralizing Antibodies
/ immunology
Cell Line, Tumor
Hepacivirus
/ genetics
Hepatitis C
/ prevention & control
Humans
Immunogenicity, Vaccine
Neutralization Tests
/ methods
Reproducibility of Results
Vaccine Development
Viral Envelope Proteins
/ genetics
Viral Hepatitis Vaccines
/ immunology
Broadly Neutralizing Antibodies
Hepatitis C Virus
Neutralizing Breadth
Vaccine
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
27
03
2021
revised:
05
10
2021
accepted:
06
10
2021
pubmed:
17
10
2021
medline:
23
2
2022
entrez:
16
10
2021
Statut:
ppublish
Résumé
Development of a prophylactic hepatitis C virus (HCV) vaccine will require accurate and reproducible measurement of neutralizing breadth of vaccine-induced antibodies. Currently available HCV panels may not adequately represent the genetic and antigenic diversity of circulating HCV strains, and the lack of standardization of these panels makes it difficult to compare neutralization results obtained in different studies. Here, we describe the selection and validation of a genetically and antigenically diverse reference panel of 15 HCV pseudoparticles (HCVpps) for neutralization assays. We chose 75 envelope (E1E2) clones to maximize representation of natural polymorphisms observed in circulating HCV isolates, and 65 of these clones generated functional HCVpps. Neutralization sensitivity of these HCVpps varied widely. HCVpps clustered into 15 distinct groups based on patterns of relative sensitivity to 7 broadly neutralizing monoclonal antibodies. We used these data to select a final panel of 15 antigenically representative HCVpps. Both the 65 and 15 HCVpp panels span 4 tiers of neutralization sensitivity, and neutralizing breadth measurements for 7 broadly neutralizing monoclonal antibodies were nearly equivalent using either panel. Differences in neutralization sensitivity between HCVpps were independent of genetic distances between E1E2 clones. Neutralizing breadth of HCV antibodies should be defined using viruses spanning multiple tiers of neutralization sensitivity rather than panels selected solely for genetic diversity. We propose that this multitier reference panel could be adopted as a standard for the measurement of neutralizing antibody potency and breadth, facilitating meaningful comparisons of neutralization results from vaccine studies in different laboratories.
Sections du résumé
BACKGROUND & AIMS
Development of a prophylactic hepatitis C virus (HCV) vaccine will require accurate and reproducible measurement of neutralizing breadth of vaccine-induced antibodies. Currently available HCV panels may not adequately represent the genetic and antigenic diversity of circulating HCV strains, and the lack of standardization of these panels makes it difficult to compare neutralization results obtained in different studies. Here, we describe the selection and validation of a genetically and antigenically diverse reference panel of 15 HCV pseudoparticles (HCVpps) for neutralization assays.
METHODS
We chose 75 envelope (E1E2) clones to maximize representation of natural polymorphisms observed in circulating HCV isolates, and 65 of these clones generated functional HCVpps. Neutralization sensitivity of these HCVpps varied widely. HCVpps clustered into 15 distinct groups based on patterns of relative sensitivity to 7 broadly neutralizing monoclonal antibodies. We used these data to select a final panel of 15 antigenically representative HCVpps.
RESULTS
Both the 65 and 15 HCVpp panels span 4 tiers of neutralization sensitivity, and neutralizing breadth measurements for 7 broadly neutralizing monoclonal antibodies were nearly equivalent using either panel. Differences in neutralization sensitivity between HCVpps were independent of genetic distances between E1E2 clones.
CONCLUSIONS
Neutralizing breadth of HCV antibodies should be defined using viruses spanning multiple tiers of neutralization sensitivity rather than panels selected solely for genetic diversity. We propose that this multitier reference panel could be adopted as a standard for the measurement of neutralizing antibody potency and breadth, facilitating meaningful comparisons of neutralization results from vaccine studies in different laboratories.
Identifiants
pubmed: 34655573
pii: S0016-5085(21)03624-6
doi: 10.1053/j.gastro.2021.10.005
pmc: PMC8792218
mid: NIHMS1748886
pii:
doi:
Substances chimiques
Antigens, Viral
0
Broadly Neutralizing Antibodies
0
Viral Envelope Proteins
0
Viral Hepatitis Vaccines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
562-574Subventions
Organisme : NIAID NIH HHS
ID : U19 AI159822
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127469
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI079031
Pays : United States
Organisme : Medical Research Council
ID : MC_UU12014/2
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : T32 AI125186
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12014/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U19 AI123862
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI151353
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132213
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12014/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801169
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : T32 GM007309
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136577
Pays : United States
Organisme : NIAID NIH HHS
ID : R24 AI158193
Pays : United States
Organisme : Medical Research Council
ID : MR/R010307/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U19 AI123861
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI088791
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 AGA Institute. All rights reserved.
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