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| DEVELOPMENT OF A LIPOPEPTIDE-BASED THERAPEUTIC VACCINE TO TREAT CHRONIC HBV INFECTION .1. INDUCTION OF A PRIMARY CYTOTOXIC T-LYMPHOCYTE RESPONSE IN HUMANS |
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| Author(s): VITIELLO A, ISHIOKA G, GREY HM, ROSE R, FARNESS P, LAFOND R, YUAN LL, CHISARI FV, FURZE J, BARTHOLOMEUZ R, CHESNUT RW |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 95 Issue: 1 Pages: 341-349 Published: JAN 1995 |
| Times Cited: 275 References: 42 |
| 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 toroid peptide 830-843 as the T helper peptide, and two palmitic acid molecules as the lipids. A dose escalation trial (5, 50, and 500 mu g) 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-mu g dose. |
| Document Type: Article |
| Language: English |
Addresses:
1. CYTEL CORP, DEPT CLIN DEV, SAN DIEGO, CA 92001 USA
2. CYTEL CORP, DEPT IMMUNOL, SAN DIEGO, CA 92001 USA
3. SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: QA882 |
| ISSN: 0021-9738 |
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