Advertisement

Research Article Free access | 10.1172/JCI117662

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

A Vitiello, G Ishioka, H M Grey, R Rose, P Farness, R LaFond, L Yuan, F V Chisari, J Furze, and R Bartholomeuz

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Vitiello, A. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Ishioka, G. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Grey, H. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Rose, R. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Farness, P. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by LaFond, R. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Yuan, L. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Chisari, F. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Furze, J. in: JCI | PubMed | Google Scholar

Department of Immunology, Cytel Corporation, San Diego, California 92001.

Find articles by Bartholomeuz, R. in: JCI | PubMed | Google Scholar

Published January 1, 1995 - More info

Published in Volume 95, Issue 1 on January 1, 1995
J Clin Invest. 1995;95(1):341–349. https://doi.org/10.1172/JCI117662.
© 1995 The American Society for Clinical Investigation
Published January 1, 1995 - Version history
View PDF
Abstract

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.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (January 1, 1995): No description
Advertisement
Advertisement