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Vitiello, A. et al.

Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.

Our goal is to use peptide epitopes that are recognized by cytotoxic T lymphocytes (CTL) as immunogens for the development of prophylactic and therapeutic vaccines with chronic hepatitis B virus (HBV) infection being our first therapeutic target. Because most CTL peptide epitopes are poor immunogens, we specifically modified them by covalently attaching two additional components: a T helper peptide epitope and two lipid molecules. Using the murine influenza virus CTL epitope NP 147-155 as a model system, we found this construct to be highly immunogenic, and a single injection resulted in memory CTL induction that persisted for > 1 yr. Based on the animal studies, a vaccine was designed and tested for both safety and its ability to induce a primary CTL response in normal subjects. The three vaccine components included HBV core antigen peptide 18-27 as the CTL epitope, tetanus toxoid peptide 830-843 as the T helper peptide, and two palmitic acid molecules as the lipids. A dose escalation trial (5, 50, and 500 micrograms) carried out in 26 normal subjects showed that the vaccine was safe and able to induce a primary HBV-specific CTL response. A dose-response curve was observed and five out of five subjects responded to the 500-micrograms dose.[1]

References

Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans. Vitiello, A., Ishioka, G., Grey, H.M., Rose, R., Farness, P., LaFond, R., Yuan, L., Chisari, F.V., Furze, J., Bartholomeuz, R. J. Clin. Invest. (1995) [Pubmed]

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