LONG-STANDING PROTECTION OF MACAQUES AGAINST CELL-FREE HIV-2 WITH A HIV-2 ISCOM VACCINE

We investigated the capacity of two immunostimulating-complex (iscom) formulations including inactivated native HIV-2 viral proteins and sel ected peptides to induce protective immunity against HIV-2 in a nonhum an primate. Four cynomolgus monkeys were first immunized with five i.m . injections of purified detergent-disrupted HIV-2 virions (total dose , 0.7 mg) in iscoms over a period of 16 months. At months 18 and 20, a ll four macaques were given booster immunizations with iscom-coupled V 3-derived synthetic peptides representing a dominating neutralizing re gion of HIV-2 gp125. Two weeks after the final dose of vaccine, the fo ur vaccinated animals, together with four controls, were challenged i. v. with 10 monkey infectious doses (MID(50)) of monkey-cell-grown homo logous cell-free virus, HIV-2(SBL-6669/H5). After the challenge, the f our control animals became readily infected; however, three of four va ccinated animals were protected as shown by repeated negative virus is olations and negative polymerase chain reaction for viral DNA and by f ailure to transmit HIV-2 infection with whole blood and lymph node cel ls into naive cynomolgus macaques. One of three protected animals show ed an anamnestic antibody response to a dominating antigenic site, ind icating possible limited virus replication. The vaccine-protected monk eys were subsequently resistant to rechallenge infection at 12, 15, an d 18 months after the first challenge, suggesting that a reasonable du ration of protective immunity had been induced by the vaccine.