7th Conference - Abstract 819

Correlation of Vaccine-Induced Cross-Tropic In Vitro Resistance to HIV-1_BaL with CTL Activity

R. JOHN¹, S. ARANGO-JARAMILLO¹, R. C. CASTILLO¹, K. WEINHOLD², and D. SCHWARTZ*¹. ¹The Johns Hopkins Sch. of Publ. Hlth., Baltimore, MD; and ²Duke Univ. Med. Ctr., Durham, NC

We have developed an in vitro challenge assay in which PBMC resistance to HIV-1_BaL correlates with naturally acquired resistance in vivo. This assay has been validated in long term non progressors, exposed uninfected, and HIV-2 infected individuals. Furthermore, statistically significant resistance was detected among selected recipients of ALVAC HIV vaccines. We have now extended this assay to a random sample of volunteers from AVEG protocols 022 and 022A (ALVAC vCP205 canarypox vector vaccine containing env, gag, and pol, with or without SF2 rgp120 boosting). A total of 59 vaccine recipients were assayed at month 10 of the study after receiving 3-5 ALVAC vaccinations and 1 rgp120 boost (depending on study arm). Volunteers' PBMC samples were classified as resistant if less than half of 6-8 replicate cultures were p24 positive on day 10. Resistance was significantly correlated with contemporaneous CTL activity: among CTL(+) volunteers, 7/22 were resistant vs. 4/37 among CTL(-) volunteers (p < 0.01). Resistance did not correlate with the presence of CTL at prior time points, suggesting that the correlation is tightly regulated temporally, and perhaps biologically. CTL activity directed against env, pol and gag epitopes was examined for association with resistance. Only correlation between contemporaneous gag-specific CTL activity and resistance approached significance: 4/11 resistant volunteers were gag CTL(+) vs. 7/48 susceptible volunteers (p = 0.1). These data indicate that a validated in vitro correlate of resistance to HIV was induced by vaccination with a multigene ALVAC vector, though only among a third of volunteers with simultaneously detectable CTL responses. Additionally, gag specific CTL showed a trend towards better correlation with resistance. It is worth noting that the vaccine prototypes were X4 IIIB, MN and SF2, whereas we measured resistance to the prototype R5 isolate BaL.

Key Words: ctl, in vitro correlates, vaccine