PROTECTION AGAINST LETHAL SIMIAN IMMUNODEFICIENCY VIRUS SIVSMMPBJ14 DISEASE BY A RECOMBINANT SEMLIKI FOREST VIRUS GP160 VACCINE AND BY A GP120 SUBUNIT VACCINE

Infection of pigtail macaques with SIVsmmPBj14, biological clone 3 (SI V-PBj14-bcl3), produces an acute and usually fatal shock-like syndrome 7 to 14 days after infection. We used this simian immunodeficiency vi rus (SIV) model as a rapid and rigorous challenge to evaluate the effi cacy of two SIV Env vaccine strategies, Groups of four pigtail macaque s were immunized four times over a 25-week span with either a recombin ant Semliki Forest virus expressing the SIV-PBj14 Env gp160 (SFV-SIVgp 160) or purified recombinant SIV-PBj14 gp120 (rgp120) in SBN-1 adjuvan t. Antibody titers to SN Env developed in all immunized animals (mean peak titers prior to challenge, 1:1,700 for SFV-SIVgp160 and 1:10,500 for rgp120), but neither neutralizing antibodies nor SIV-specific T-ce ll proliferative responses were detectable in any of the vaccinees. Al l macaques were challenged with a 100% infectious, 75% fatal dose of S IV-PBj14-bcl3 at week 26. Three of four control animals died of acute SIV-PBj14 syndrome on days 12 and 13. By contrast, all four SFV-SIVgp1 60-immunized animals and three of the four rgp120-immunized animals we re protected from lethal disease. While all virus-challenged animals b ecame infected, symptoms of the SIV-PBj14 syndrome were more severe in controls than in vaccinees. Mean virus titers in plasma at 13 days po stchallenge were approximately 10-fold lower in vaccinated than contro l animals. However, there was no apparent correlation between survival and levels of peripheral blood mononuclear cell-associated culturable virus, provirus load, or any antiviral immunologic parameter examined . The results indicate that while immunization with SFV-SIVgp160 and r gp120 did not protect against virus infection, these Env vaccines did lower the virus load in plasma and protect against the lethal SIV-PBj1 4 challenge.