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A novel therapeutic HBV vaccine induces potent surface‐ and core‐specific immunogenicity in mice rhesus macaques
Author(s) -
Gesner Marianne L,
Heeke Darren S,
Martins Eduardo,
Livingston Brian S,
Van Nest Gary,
Marshall Jason D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.859.12
Subject(s) - hbcag , hbsag , elispot , immunology , virology , antigen , immunogenicity , medicine , immune system , hepatitis b virus , antibody , adjuvant , cd8 , virus
HBV infects approximately 350 million people worldwide, and carriers are at increased risk for cirrhosis and hepatocellular carcinoma. Current HBV therapies do not eradicate HBV and have limited long‐term efficacy. We have developed a novel immunotherapeutic vaccine for treatment of chronic HBV infection. The vaccine, composed of HBsAg (HBV surface antigen), HBcAg (HBV core antigen) and a proprietary adjuvant, was designed to induce virus‐specific cellular immune responses such as are typically correlated with HBV clearance. Mice immunized with the vaccine exhibited robust cellular and humoral immune responses to both HBcAg and HBsAg. Cell‐mediated responses, as determined by ELISPOT and intracellular cytokine staining (ICS), demonstrated that CD8 T cell responses were dominated by HBcAg‐specific immunity, while the majority of the CD4 response was HBsAg‐directed. The vaccine also elicited strong anti‐HBsAg and anti‐HBcAg immunoglobulin responses in both IgG1 and IgG2a isotypes. In rhesus macaques, 4 monthly immunizations induced high frequencies of antigen‐specific IFN‐g/IL‐2‐secreting T cells in response to HBsAg and HBcAg overlapping peptide pools as measured by ELISPOT and ICS. Vaccinated rhesus also exhibited >10 5 mIU/mL anti‐HBsAg Ig, after only two immunizations, and substantial levels of anti‐HBcAg Ig as well. These data suggest this dual‐antigen immunotherapeutic vaccine may be valuable in the treatment of chronic HBV infection.