Repeated exposure to heterologous hepatitis C viruses associates with enhanced neutralizing antibody breadth and potency.
Adaptive immunity
Antigen
Hepatitis
Immunology
Virology
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
01 08 2022
01 08 2022
Historique:
received:
09
03
2022
accepted:
17
05
2022
pubmed:
20
5
2022
medline:
3
8
2022
entrez:
19
5
2022
Statut:
ppublish
Résumé
A prophylactic hepatitis C virus (HCV) vaccine that elicits neutralizing antibodies could be key to HCV eradication. However, the genetic and antigenic properties of HCV envelope (E1E2) proteins capable of inducing anti-HCV broadly neutralizing antibodies (bNAbs) in humans have not been defined. Here, we investigated the development of bNAbs in longitudinal plasma of HCV-infected persons with persistent infection or spontaneous clearance of multiple reinfections. By measuring plasma antibody neutralization of a heterologous virus panel, we found that the breadth and potency of the antibody response increased upon exposure to multiple genetically distinct infections and with longer duration of viremia. Greater genetic divergence between infecting strains was not associated with enhanced neutralizing breadth. Rather, repeated exposure to antigenically related, antibody-sensitive E1E2s was associated with potent bNAb induction. These data reveal that a prime-boost vaccine strategy with genetically distinct, antibody-sensitive viruses is a promising approach to inducing potent bNAbs in humans.
Identifiants
pubmed: 35588376
pii: 160058
doi: 10.1172/JCI160058
pmc: PMC9337827
doi:
pii:
Substances chimiques
Antibodies, Neutralizing
0
Broadly Neutralizing Antibodies
0
Hepatitis C Antibodies
0
Viral Envelope Proteins
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
Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM136577
Pays : United States
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 : R21 AI151353
Pays : United States
Organisme : NIAID NIH HHS
ID : R00 AI153465
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI088791
Pays : United States
Commentaires et corrections
Type : CommentIn
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