OUTCOME OF IMMUNIZATION OF CYNOMOLGUS MONKEYS WITH RECOMBINANT SEMLIKI-FOREST-VIRUS ENCODING HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE PROTEIN AND CHALLENGE WITH A HIGH-DOSE OF SHIV-4 VIRUS

Infection of macaques with chimeric simian-human immunodeficiency viru ses (SHIVs) allows evaluation of HIV-1 envelope vaccines, SHIV-4 is ba sed on SIVmac239 but carries the env, tat, and rev genes of HIV-1(IIIB ). In this study we used Semliki Forest virus (SFV) RNA vectors to exp ress the envelope protein gp160 of HIV-1(IIIB) in cynomolgus macaques. Monkeys were immunized four times with recombinant suicide SFV, Where as two of four monkeys showed T cell-proliferative responses, only one monkey had demonstrable levels of antibodies to HIV-1 gp41 and gp120 as shown by enzyme-linked immunosorbent assay (ELISA) and Western blot , The vaccinated monkeys and four control animals were challenged with 10,000 MID100 (100% minimum infectious doses) of cell-free monkey cel l-grown SHIV-4 virus, As demonstrated by virus isolation, all macaques became infected after challenge, All vaccinated monkeys showed an HIV -l-specific anamnestic T cell-proliferative response, Three of four va ccinees had developed HIV-l-Env-specific antibodies 2 weeks after chal lenge whereas none of the four controls showed any detectable immune r esponse at this time point. Furthermore, three of four vaccinated monk eys had no demonstrable viral antigenemia and low viral load as oppose d to one of the four naive control animals.