Mimotopes of the hyper variable region 1 of the hepatitis C virus induce cross-reactive antibodies directed against discontinuous epitopes.
Hepatitis C virus (HCV) is a major cause worldwide of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, and the development of an effective vaccine represents a high priority goal. The hyper variable region 1 (HVR1) of the second envelope protein (E2) of HCV contains a principal neutralizing determinant, but it is highly variable among different isolates and it is involved in the escape from host immune response. To be effective, a vaccine should elicit a cross-reacting humoral response against the majority of viral variants. We show that it is possible to achieve a broadly cross-reactive immune response in rabbits by immunization with mimotopes of the HVR1, selected from a specialized phage library using HCV patients' sera. Some of the cross-reacting anti-mimotope antibodies elicited in rabbits, recognize discontinuous epitopes in a manner similar to those induced by the virus in infected patients.
Roccasecca
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R
Istituto di Ricerche di Biologia Molecolare "P. Angeletti", Via Pontina Km 30.600, 00040 Pomezia, Rome, Italy.
Folgori
A
A
Ercole
B B
BB
Puntoriero
G
G
Lahm
A
A
Zucchelli
S
S
Tafi
R
R
Pezzanera
M
M
Galfre
G
G
Tramontano
A
A
Mondelli
M U
MU
Pessi
A
A
Nicosia
A
A
Cortese
R
R
Meola
A
A
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000918:Antibody Specificity; D003429:Cross Reactions; D005260:Female; D018937:Hepatitis C Antibodies / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D019151:Peptide Library; D011817:Rabbits; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D018937:Hepatitis C Antibodies; D016056:Immunodominant Epitopes; D019151:Peptide Library; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C091015:glycoprotein E2, Hepatitis C virus