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 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.
Frasca
Loredana
L
Department of Cellular and Developmental Biology, La Sapienza University, Rome, Italy.
Scottà
Cristiano
C
Del Porto
Paola
P
Nicosia
Alfredo
A
Pasquazzi
Caterina
C
Versace
Ilaria
I
Masci
Anna Maria
AM
Racioppi
Luigi
L
Piccolella
Enza
E
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D022801:Complementarity Determining Regions; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D022801:Complementarity Determining Regions; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell