HIGHLY ATTENUATED SIVMAC142 IS IMMUNOGENIC BUT DOES NOT PROTECT AGAINST SIVMAC251 CHALLENGE

We report here the use of the highly attenuated SIVmac142 clone, unabl e to establish permanent infection of rhesus macaques, in a vaccine tr ial. Four rhesus macaques were immunized over a long time period with HUT-78 cells infected with wild-type SIVmac142 or, in order to reinfor ce the safety use of the vaccine, a deleted mutant with similar in vit ro infectivity. The first two injections were done with living cells a nd the remaining boosts with cells emulsified in muramyl dipeptide adj uvant. Three control macaques were injected with uninfected HUT-78 cel ls. Over 3 years, we have been unable except once to detect viral infe ctions by three methods. However, antibodies directed against the vira l Gag proteins and envelope glycoproteins were detected by immunoblots and/or in vitro neutralization assays. All macaques were challenged i ntravenously with a low dose (10 animal infectious doses) of a highly pathogenic biological clone of SIVmac251 grown on macaque PBMCs. All s even animals became persistently viremic following challenge. The cell -associated viral loads of the vaccinated monkeys were not reduced rel ative to those of unvaccinated controls during the first weeks postcha llenge even if vaccinated monkeys did not present a transient CD4 decr ease. Thus, our data reinforced the notion that the efficacy of live a ttenuated SIV requires the establishment of persistent infection.