Antibody-selected mimics of hepatitis C virus hypervariable region 1 activate both primary and memory Th lymphocytes.

Published

Journal Article

An ideal strategy that leads to a vaccine aimed at controlling viral escape may be that of preventing the replication of escape mutants by eliciting a T- and B-cell repertoire directed against many viral variants. The hypervariable region 1 (HVR1) of the putative envelope 2 protein that presents B and T epitopes shown to induce protective immunity against hepatitis C virus (HCV), might be suitable for this purpose if its immunogenicity can be improved by generating mimics that induce broad, highly cross-reactive, anti-HVR1 responses. Recently we described a successful approach to select HVR1 mimics (mimotopes) incorporating the variability found in a great number of viral variants. In this report we explore whether these mimotopes, designed to mimic B-cell epitopes, also mimic helper T-cell epitopes. The first interesting observation is that mimotopes selected for their reactivity to HVR1-specific antibodies of infected patients also do express HVR1 T-cell epitopes, suggesting that similar constraints govern HVR1-specific humoral and cellular immune responses. Moreover, some HVR1 mimotopes stimulate a multispecific CD4(+) T-cell repertoire that effectively cross-reacts with HVR1 native sequences. This may significantly limit effects as a T-cell receptor (TCR) antagonist frequently exerted by natural HVR1-variants on HVR1-specific T-cell responses. In conclusion, these data lend strong support to using HVR1 mimotopes in vaccines designed to prevent replication of escape mutants.

Full Text

Duke Authors

Cited Authors

  • Frasca, L; Scottà, C; Del Porto, P; Nicosia, A; Pasquazzi, C; Versace, I; Masci, AM; Racioppi, L; Piccolella, E

Published Date

  • September 2003

Published In

Volume / Issue

  • 38 / 3

Start / End Page

  • 653 - 663

PubMed ID

  • 12939592

Pubmed Central ID

  • 12939592

International Standard Serial Number (ISSN)

  • 0270-9139

Digital Object Identifier (DOI)

  • 10.1053/jhep.2003.50387

Language

  • eng

Conference Location

  • United States