HIGHLY ATTENUATED HTLV TYPE I-ENV POXVIRUS VACCINES INDUCE PROTECTIONAGAINST A CELL-ASSOCIATED HTLV TYPE-I CHALLENGE IN RABBITS

The entire envelope protein of the human T cell leukemia/lymphoma viru s type I (HTLV-I)(1711), obtained from the DNA of a West African healt hy HTLV-I-infected patient, was expressed in the highly attenuated pox virus vaccine vectors ALVAC and NYVAC. These live recombinant vaccine candidates were used to immunize New Zealand White rabbits. Immunizati on regimens included inoculation of the poxvirus recombinant alone as well as prime/boost protocols using gp63 HTLV-I envelope precursor pro tein in Alum as the subunit boost. All animals were exposed to an HTLV -I cell-associated challenge (5 x 10(4) cells) from a primary culture of the HTLV-I-BOU isolate. The results indicated that two inoculations of the ALVAC-based HTLV-I-env vaccine candidate protected animals aga inst viral challenge 5 months following the last immunization. However , a combination protocol with ALVAC-env and two additional boosts of g p63 surprisingly failed to confer protection, suggesting that administ ration of the subunit preparation might be deleterious. Further, in th e case of the NYVAC HTLV-I-env recombinant, protection was afforded as early as 2 months following the first immunization. Last, all the pro tected animals in the NYVAC and ALVAC trials were challenged 5 months following the initial challenge exposure with 5 mi of blood from an HT LV-I-BOU-infected animal, and subsequently became infected. Protection conferred by the attenuated HTLV-I-env recombinant poxvirus vaccine i n the rabbit model might be instrumental for optimizing the immunogeni city of poxvirus-based vaccine candidates against human immunodeficien cy virus (HIV), particularly because of the need to enhance protection against cell-to-cell transmission. This approach has already shown so me efficacy in the HIV type 2/rhesus macaque system.