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

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 a...

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Published in:Hepatology (Baltimore, Md.) Md.), 2003-09, Vol.38 (3), p.653-663
Main Authors: Frasca, Loredana, Scottà, Cristiano, Del Porto, Paola, Nicosia, Alfredo, Pasquazzi, Caterina, Versace, Ilaria, Masci, Anna Maria, Racioppi, Luigi, Piccolella, Enza
Format: Article
Language:English
Subjects:
Adult
Aged
B-Lymphocytes - immunology
Biological and medical sciences
Cell Line
Complementarity Determining Regions
Cross Reactions
Epitopes - analysis
Female
Hepacivirus - genetics
Hepatitis C, Chronic - immunology
Hepatitis C, Chronic - virology
Human viral diseases
Humans
Immunologic Memory - immunology
Infectious diseases
Lymphocyte Activation - immunology
Lymphocytes - immunology
Male
Medical sciences
Middle Aged
Molecular Mimicry - immunology
Receptors, Antigen, T-Cell - antagonists & inhibitors
T-Lymphocytes - immunology
T-Lymphocytes, Helper-Inducer - immunology
Viral diseases
Viral hepatitis
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Summary: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. (H epatology 2003;38:653-663.)
ISSN:0270-9139
1527-3350
DOI:10.1053/jhep.2003.50387