Mimotopes of the hepatitis C virus hypervariable region 1, but not the natural sequences, induce cross-reactive antibody response by genetic immunization
Autor: | Giovanni Galfre, Riccardo Cortese, Rosalba Tafi, Silvia Zucchelli, Bruno Bruni Ercole, Alfredo Nicosia, Jean Dubuisson, Annalisa Meola, Rosamaria Roccasecca |
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Přispěvatelé: | S. Zucchelli, R. Roccasecca, A. Meola, B. B. Ercole, R. Tafi, J. Dubuisson, G. Galfre, R. Cortese, A. Nicosia |
Rok vydání: | 2001 |
Předmět: |
viruses
Molecular Sequence Data Immunoglobulin Variable Region Hepacivirus Cross Reactions Active immunization Antibodies Viral Injections Intramuscular Epitope Cell Line Epitopes PLASMID DNA IMMUNE-RESPONSES CELL-SURFACE ENVELOPE E2 GLYCOPROTEIN PROTEIN VACCINATION HCV CHIMPANZEES Antigen Humans Amino Acid Sequence Hepatology biology Mimotope Molecular Mimicry virus diseases Virology digestive system diseases Recombinant Proteins Hypervariable region Epitope mapping Ectodomain Genetic Techniques Antibody Formation DNA Viral biology.protein Immunization Antibody Plasmids |
Zdroj: | Hepatology (Baltimore, Md.). 33(3) |
ISSN: | 0270-9139 |
Popis: | The hypervariable region 1 (HVR1) of the putative envelope protein E2 of hepatitis C virus (HCV) contains a principal neutralization epitope, and anti-HVR1 antibodies have been shown to possess protective activity in ex vivo neutralization experiments. However, the high rate of variability of this antigenic fragment may play a major role in the mechanism of escape from host immune response and might represent a major obstacle to developing an HCV vaccine. Thus, even if direct experimental evidence of the neutralizing potential of anti-HVR1 antibodies by active immunization is still missing, the generation of a vaccine candidate with a cross-reactive potential would be highly desirable. To overcome the problem of HVR1 variability, we have engineered cross-reactive HVR1 peptide mimics (mimotopes) at the N terminus of the E2 ectodomain in plasmid vectors suitable for genetic immunization. High levels of secreted and biologically active mimotope/E2 chimeras were obtained by transient transfection of these plasmids in cultured cells. All plasmids elicited anti-HVR1 antibodies in mice and rabbits with some of them leading to a cross-reacting response against many HVR1 variants from natural isolates. Epitope mapping revealed a pattern of reactivity similar to that induced by HCV infection, In contrast, plasmids encoding naturally occurring HVR1 sequences displayed either on full-length E2 in the context of the whole HCV structural region, or on a soluble, secreted E2 ectodomain, did not induce a cross-reacting anti-HVR1 response. |
Databáze: | OpenAIRE |
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