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A self‐adjuvanting multiepitope immunogen that induces a broadly cross‐reactive antibody to hepatitis C virus
Author(s) -
Torresi Joseph,
Stock Owen M.,
Fischer Alexandra E.,
Grollo Lara,
Drummer Heidi,
Boo Irene,
Zeng Weiguang,
EarnestSilveira Linda,
Jackson David C.
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21538
Subject(s) - epitope , immunogen , virology , antibody , lipopeptide , biology , hepatitis c virus , antiserum , titer , monoclonal antibody , virus , immunology , genetics , bacteria
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. Conclusion : 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. (H EPATOLOGY 2007;45:911–920.)