Induction of cross-reactive humoral immune response by immunization with mimotopes of the hypervariable region 1 of the hepatitis C virus.
Hepatitis C Virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, worldwide, 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. Thus, 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. At least 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
R
R
Istituto di Ricerche di Biologia Molecolare P. Angeletti, Pomezia, Roma, 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; D000818:Animals; D000940:Antigenic Variation; D003429:Cross Reactions; D018604:Epitope Mapping; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000096:biosynthesis*; D006801:Humans; D007114:Immunization; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011817:Rabbits; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus