View All Abstracts for Session 58
317 rMamu-IL-12 Conditioning during Acute SIVmac251 Infection Leads to Decreased Viral Loads and Prolonged Survival
A. A. Ansari*, A. E. Mayne, J. B. Sundstrom, P. Bostik, B. Grimm, and F. Villinger
Emory Univ. Sch. of Med., Atlanta, GA, USA
In efforts to evaluate the potential of IL-12 to enhance virus-specific TH1 response, groups of macaques (n = 4) were conditioned with either high doses (20 mug/kg, day (2 and 0) or low doses (10 mug/kg,day (2, 0) of recombinant macaque IL-12 subQ. Two days following the initial IL-12 administration, all monkeys and 4 untreated controls were inoculated with SIVmac251 IV. The high and low doses were then given IL-12 for 8 weeks 2 times per week at 10 and 2 mug/kg resp. Although control monkeys all developed AIDS by 8 months, all monkeys given high dose of IL-12 were alive and healthy at 20 months p.i. Three out of the 4 monkeys administered low IL-12 doses had developed AIDS by 10 months p.i. Treatment with high doses of IL-12 resulted in lower acute plasma viral loads and significantly lower plasma viral set points (1(2 logs), associated with significant enhancement of SIVgag/pol pCTL frequencies but only modest enhancement of SIVenv pCTL frequencies over control animals. There was also a significant decrease in PBMC proviral loads in the high dose IL-12 treated monkeys as well as barely detectable proviral loads in peripheral lymph nodes, whereas control animals showed 700(1,600 DNA copies per 105 LNC. In addition, high dose IL-12 treatment prevented the rapid loss of tetanus toxoid and KLH-specific memory proliferative responses as well as influenza-specific memory pCTLs, which were in contrast lost in the control monkeys. Humoral responses to these nominal antigens did not differ between the 3 groups. Of further interest was the finding that, whereas in control monkeys, CD8alphabeta+ T cells were responsible for secretion of soluble virus inhibitory factors, in IL-12 treated monkeys, CD8alphaalpha T cells appeared to contribute to such antiviral mechanism at 6 weeks p.i. but not at later time points. These results suggest that IL-12 induced skewing of the immune milieu during acute pathogenic SIV infection had a profound influence on antiviral responses, viral loads and distribution, memory immune responses, and survival.
Contact Author about this Abstract
