HIGHLY ATTENUATED HIV TYPE-2 RECOMBINANT POXVIRUSES, BUT NOT HIV-2 RECOMBINANT SALMONELLA VACCINES, INDUCE LONG-LASTING PROTECTION IN RHESUS MACAQUES

Immunization schemes employing priming with vector-based vaccine candi dates followed by subunit booster administrations have been explored a nd shown to have merit in the human immunodeficiency virus type 1 (HIV -1) and simian immunodeficiency virus systems, In this study, we have assessed the priming capacity of highly attenuated poxvirus vector (NY VAC and ALVAC)-based HIV-2 recombinants, as well as Salmonella typhimu rium HIV-2 recombinants in rhesus macaques, ALVAC- and NYVAC-based vac cine candidates expressing the HIV-2 gag, pol, and env genes or NYVAC- based recombinants expressing either gp160 or gp120 were used to immun ize rhesus macaques in combination protocols with alum-adjuvanted HIV- 2 rgp160, Following intravenous challenge exposure with 100 infectious doses of the HIV-2(SBL6669) parental virus genotype mixture, seven of eight animals were protected from infection. The seven protected anim als were rechallenged 6 months postprimary challenge, without addition al booster inoculations, with the same dose of the HIV-2(SBL6669) pare ntal virus. Five of the seven animals remained protected against HIV-2 infection at 6 months following the second challenge. In contrast, or al immunization with recombinant Salmonella expressing the HIV-2 gag a nd the gp120 portion of the envelope either alone or in combination wi th alum-adjuvanted rgp160 failed to confer protection. These results s uggest that the NYVAC- and ALVAC-based recombinants may confer long-la sting protection and that these two highly attenuated poxvirus vaccine vectors may represent promising candidates for developing an acquired immunodeficiency syndrome vaccine.