ENHANCEMENT OF MHC CLASS I-RESTRICTED PEPTIDE-SPECIFIC T-CELL INDUCTION BY A DNA PRIME MVA BOOST VACCINATION REGIME

Human immunodeficiency virus (HIV) vaccine candidates were previously constructed as a string of cytotoxic T lymphocyte (CTL) epitopes deliv ered and expressed using DNA and modified virus Ankara (MVA; an attenu ated vaccinia virus) vectors. These vaccines were shown to induce inte rferon (IFN)-gamma-producing and cytolytic CD8(+) T cells after a sing le vaccine administration. In the course of this work, immunization pr otocols were sought which would improve the levels of induced HIV-spec ific T cells. It was found that previous immunological exposure to MVA reduced the efficiency of subsequent priming and boosting using the s ame vaccine vehicle. However a combined regime whereby the animals wer e first primed with the DNA vaccine and then boosted with MVA was the most potent protocol for the induction of both interferon-gamma-produc ing and cytolytic T cells against two CTL epitopes simultaneously. The general applicability of this novel vaccination method for induction of major histocompatibility complex class I-restricted T cells is disc ussed. (C) 1998 Elsevier Science Ltd. All rights reserved.