Abstracts

Abstract presented at Sixth Annual Conference on Vaccine Research - May 5-7, 2003, Arlington, VA

An Hsp65-HBV Core Antigen Fusion Protein Primes HBcAg-Specific CTL Responses in Immunologically Tolerant HBV Transgenic Mice

L.S.D. Anthony(1), S.G. Winslow(2), H. Liu(1), G. Rowse(1), B. Wu(1), A. Recktenwald(1), J.G. Julander(2), L.A. Mizzen(1), J.D. Morrey(2), M.I. Siegel(3)

1. Stressgen Biotechnologies Corporation, Victoria B.C. Canada
2. Utah State University, Logan UT, USA
3. Stressgen Biotechnologies Inc., Collegeville, PA USA

In individuals with chronic hepatitis B virus (HBV) infection, viral persistence is thought to be related to insufficient HBV-specific CTL responses. Therefore, immunotherapies inducing effective HBV-specific CTL may promote resolution of infection. Recombinant CoValTM fusion proteins generated from antigens fused to heat shock proteins (Hsp) prime potent CTL activity in mice. HspBcor is a CoValTM fusion protein engineered from HBV core antigen (HBc) and Hsp65 from Mycobacterium bovis BCG. Restimulated splenocytes from C57BL/6 mice immunized with HspBcor in buffer saline displayed a high level of H-2Kb-restricted lytic activity, whereas cells from mice immunized with HBc antigen alone did not. HspBcor was similarly effective at eliciting HLA-A2-restricted CTL in HLA-A2Kb transgenic mice. HspBcor-primed CTL lysed both peptide-pulsed and HBc-transfected target cells, which express HBc endogenously. IFN-?, a cytokine implicated in CTL-mediated inhibition of hepatic viral gene expression, was also released by HspBcor-primed CTL. Induction of CTL was further evaluated in HBV transgenic mice, which are commonly employed as a model of chronic HBV infection. A single injection of HspBcor was observed to elicit CTL in some, but not all, transgenic mice, which are immunologically tolerant to HBV antigens due to in utero exposure. These data support the hypothesis that the CoValTM fusion protein, HspBcor, will be an effective agent in the immunotherapy of chronic HBV infection.