Exploiting information inherent in binding sites of virus-specific antibodies: design of an HCV vaccine candidate cross-reactive with multiple genotypes.
OBJECTIVE
The role of antibody in hepatitis C virus (HCV) infection remains unclear although many reports attest to its role in viral clearance. Here we describe epitopes that are recognized by antibody present in the serum of infected patients and show that such epitopes can induce neutralizing antibodies.


METHODS
Human serum containing hyperimmune anti-HCV IgG was used to extract epitopes from a library of synthetic peptides that encompassed the sequences of the E1 and E2 proteins of HCV genotype 1a H77. Peptides that were bound by IgG were identified by mass spectrometry. Assembly of these epitopes with a helper T cell determinant was then carried out in order to construct candidate epitope-based vaccines.


RESULTS
Three distinct antigenic sites were defined in the E1E2 glycoproteins by epitopes identified by antibody present in infected individuals. Four of the peptide epitopes identified are conserved in at least three HCV genotypes and are bound by antibody present in the sera of chronically infected and convalescent individuals. Synthetic vaccines based on these epitopes elicited antibodies that are capable of (i) capturing HCV virions from the serum of viraemic patients and (ii) inhibiting HCV pseudovirus particle entry into Huh7 cells.


CONCLUSIONS
This approach exploits the information inherent in the binding sites of virus-specific antibodies and represents a novel method for the design of synthetic epitope-based vaccines.
Grollo
Lara
L
Cooperative Research Centre for Vaccine Technology, Department of Microbiology Et Immunology, The University of Melbourne, Parkville, VIC, Australia.
Torresi
Joseph
J
Drummer
Heidi
H
Zeng
Weiguang
W
Williamson
Nicholas
N
Jackson
David C
DC
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D003429:Cross Reactions; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000378:metabolism*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006526:Hepatitis C / Q000517:prevention & control / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019151:Peptide Library; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics
D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D019151:Peptide Library; D014761:Viral Hepatitis Vaccines; D014764:Viral Proteins