John R, Castillo R, Arango-Jaramillo S, Turner B, Iyengar S, Schwartz D; Department of Molecular Microbiology and Immunology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD.
We have previously described an in vitro challenge assay in which PBMC resistance to outgrowth of endogenous HIV correlates with resistance to exogenous inocula of CXCR4 tropic HIV-1MN and CCR5 tropic HIV-1BaL. We have subsequently validated this assay in groups of exposed uninfected individuals, some of whom are HIV-2+. In these individuals resistance to BaL was more apparent than to MN. We now report on the induction of resistance to exogenous HIV-1(BaL) and HIV-1(MN) in PBMCs of vaccinees participating in AVEG protocol 026. Two volunteers received ALVAC vCP300 canarypox vector containing env (MNgp120/LAIgp41), gag, pol, and nef gene regions at month 0 and 1, with SF2 rgp120 subunit boosting in MF59 adjuvant at months 3 and 6. Two volunteers received four doses of ALVAC 300 at 0,1, 3 and 6 or 0,1,6, and 9 months. All four volunteers were HLA A2 for at least one allele. No recipient developed in vitro resistance after only 2 ALVAC injections, even with two additional subunit envelope boosts, whereas 3 or 4 ALVAC injections without subunit boosting induced resistance to both strains of challenge virus. In all cases of resistance to viral challenge, removal of CD8+ T cells from parallel cultures resulted in excellent growth of HIV-1 MN or BaL. The molecular state of viral inocula in resistant cultures, and the ability of their supernatants to suppress HIV in control cultures has been evaluated, and results will be presented.
Keywords: AEGIS, Genes, nef, HIV-1, Vaccination, HIV Infections, HIV-2, Virus Diseases, in vitro, genetics, AIDS
