A self-adjuvanting multiepitope immunogen that induces a broadly cross-reactive antibody to hepatitis C virus.
We describe a peptide-based strategy for HCV vaccine design that addresses the problem of variability in hypervariable region 1 (HVR1). Peptides representing antibody epitopes of HVR1 from genotype 1a were synthesized and incorporated into multideterminant immunogens that also included lipid moieties and helper T (T(h)) cell epitopes. Mice inoculated with these polyepitopes generated strong antibody responses. Antibody titers were highest in mice inoculated with polyepitope immunogens which contained the lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys). Antisera were tested for their potential to neutralize HCV by 3 currently available assays. Antibodies elicited in mice by the polyepitope-based vaccine candidates were able to (1) bind to E2 expressed on the surface of E1/E2-transfected human embryonic kidney (HEK) 293T cells, (2) capture HCV of different genotypes (1, 2, and 3) from the serum of chronically infected humans in an immune capture RT-PCR assay and (3) inhibit HCVpp entry into Huh7 cells. Antibody present in the sera of patients chronically infected with HCV genotypes 1, 2, 3, and 4 also bound to the HVR1-based polyepitope.


CONCLUSIONS
These results demonstrate the potential of self-adjuvanting epitope-based constructs in the development and delivery of cross-reactive immunogens that incorporate potential neutralizing epitopes present within the viral envelope of HCV.
Torresi
Joseph
J
Department of Medicine and Clinical Centre for Research Excellence, Royal Melbourne Hospital, The University of Melbourne, Parkville 3050, Victoria, Australia. josepht@unimelb.edu.au
Stock
Owen M
OM
Fischer
Alexandra E
AE
Grollo
Lara
L
Drummer
Heidi
H
Boo
Irene
I
Zeng
Weiguang
W
Earnest-Silveira
Linda
L
Jackson
David C
DC
D000818:Animals; D000914:Antibodies, Viral; D002460:Cell Line; D000939:Epitopes; D005260:Female; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D044967:Serum / Q000276:immunology; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D000914:Antibodies, Viral; C087035:E1 protein, Hepatitis C virus; D000939:Epitopes; C400562:HVR1 protein, Hepatitis C virus; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins