CONSTRUCTION OF ATTENUATED HIV-1 ACCESSORY GENE IMMUNIZATION CASSETTES

Delivery of genetic expression cassettes into animals can effectively induce both humoral and cellular immunity to the expressed gene produc t. Previously, we used this strategy to immunize against HIV-1 structu ral and enzymatic proteins in mice, non-human primates and in humans. In contrast, the use of the accessory genes including vif, vpr, vpu an d nef as immunotherapeutic vaccine targets has not been well character ized. Our goal is to design an effective genetic HIV vaccine, which in cludes the accessory genes as part of a multi-component immunogen. In order to develop accessory genes as genetic vaccines, we have molecula rly cloned and analysed the sequence variation and immunogenic potenti al present in these genes derived from viral isolates obtained from HI V-1 infected patients and laboratory isolates. Prototype genetic varia nts were selected and their ability to induce humoral and cellular imm une responses was studied in animal models. We observed that attenuate d accessory genes can effectively induce both humoral and cellular res ponses in mice and the resulting immune response is directly correlate d with DNA concentrations delivered and the number of boosts. This str ategy can be used generally to develop an effective, safe DNA vaccine for any pathogen. (C) 1998 Published by Elsevier Science Ltd. All righ ts reserved.