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

Abstract

Infection of macaques with chimeric simian-human immunodeficiency viruses (SHIVs) allows evaluation of HIV-1 envelope vaccines. SHIV-4 is based on SIV_mac239 but carries the env, tat, and rev genes of HIV-1_IIIB. In this study we used Semliki Forest virus (SFV) RNA vectors to express the envelope protein gp160 of HIV-1_IIIB in cynomolgus macaques. Monkeys were immunized four times with recombinant suicide SFV. Whereas 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 cell-grown SHIV-4 virus. As demonstrated by virus isolation, all macaques became infected after challenge. All vaccinated monkeys showed an HIV-1-specific anamnestic T cell-proliferative response. Three of four vaccinees had developed HIV-1-Env-specific antibodies 2 weeks after challenge whereas none of the four controls showed any detectable immune response at this time point. Furthermore, three of four vaccinated monkeys had no demonstrable viral antigenemia and low viral load as opposed to one of the four naive control animals.