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

The entire envelope protein of the human T cell leukemia/lymphoma virus type I (HTLV-I)(1711), obtained from the DNA of a West African healthy HTLV-I-infected patient, was expressed in the highly attenuated poxvirus vaccine vectors ALVAC and NYVAC. These live recombinant vaccine candidates were used to immunize New Zealand White rabbits. Immunization regimens included inoculation of the poxvirus recombinant alone as well as prime/boost protocols using gp63 HTLV-I envelope precursor protein 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 against viral challenge 5 months following the last immunization. However, a combination protocol with ALVAC-env and two additional boosts of gp63 surprisingly failed to confer protection, suggesting that administration of the subunit preparation might be deleterious. Further, in the case of the NYVAC HTLV-I-env recombinant, protection was afforded as early as 2 months following the first immunization. Last, all the protected animals in the NYVAC and ALVAC trials were challenged 5 months following the initial challenge exposure with 5 mi of blood from an HTLV-I-BOU-infected animal, and subsequently became infected. Protection conferred by the attenuated HTLV-I-env recombinant poxvirus vaccine in the rabbit model might be instrumental for optimizing the immunogenicity of poxvirus-based vaccine candidates against human immunodeficiency virus (HIV), particularly because of the need to enhance protection against cell-to-cell transmission. This approach has already shown some efficacy in the HIV type 2/rhesus macaque system.