Pre-clinical development of a multi-CTL epitope-based DNA prime MVA boost vaccine for AIDS

Reliable and effective methods for induction of cytotoxic T-lymphocytes (CTL) are constantly persued. Central to this search is work in animal models, which allow to test novel vaccine strategies and ultimately lead to a more efficient planning of clinical trials. Here, human immunodeficiency virus (HIV) vaccine candidates were constructed as a string of partially overlapping CTL epitopes (20 human, 3 macaque and 1 mouse) delivered and expressed using plasmid DNA and modified virus Ankara (MVA; an attenuated vaccinia virus), which are both vaccine vehicles acceptable for use in humans. In mice, these vaccines were shown to induce virus-specific interferon-gamma-producing and cytolytic CD8(+) T-cells after a single intramuscular needle injection. When immunization protocols were sought which would improve the level of induced HIV-specific T-cells, DNA priming-MVA boosting was found to be the most potent protocol. The multi-epitope DNA also elicited CTL when delivered intradermally using the Accell(R) gene delivery device (gene gun). Finally, a combined intradermal gene gun DNA-MVA vaccination regimen induced in macaques high frequencies of circulating CTL, which were comparable to those observed in simian immunodeficiency virus (SIV)-infected monkeys. Further optimization of this method in non-human primates is under way. Thus, a vaccination regimen for an effective elicitation of CTL has been developed which might facilitate evaluation of the role(s) that these lymphocytes play in the control of SIV and HIV infections. (C) 1999 Elsevier Science B.V. All rights reserved.