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6th International AIDS ConferenceSan Francisco, California, USA — June 20-23, 1990 |
Int Conf AIDS 1990 Jun 20-23; 6:326 (abstract no. 1051)
Keefer MC, Bonnez W, Roberts NJ Jr, Lambert J, Dolin R, Reichman R; University of Rochester Medical Center, Rochester, NY, USA
OBJECTIVES: To characterize cellular immune responses to a live, vaccinia-rgp160 vaccine in healthy, low-risk, seronegative volunteers.
METHODS: As part of the NIAID AIDS Vaccine Clinical Trials Network, we enrolled 5 vaccinia-naive subjects in a phase I, randomized, escalating dose, double-blind, placebo-controlled trial of the initial dose of a vaccinia-rgp160 construct (HIVAC-le, Oncogen; Bristol-Myers Co., Wallingford, CT). Three received 2 +/- 1x10(7) pfu/ml HIVAC-le, and 2 received smallpox vaccine (Dryvax, Wyeth Labs, Marietta, PA) at time 0 and 60 days. Lymphocyte proliferation assays (LPA) were performed using cryopreserved peripheral blood mononuclear cells (PBMC) from study days 28, 90 and 180. One subject also had LPA performed using PBMC obtained longitudinally from day 0 to 120. We also examined supernatants of rgp160-stimulated PBMC cultures for alpha-interferon (alpha-IFN) production at day 180. Baculovirus-expressed recombinant rgp160 and rp24 (MicroGene Sys, West Haven, CT) were used as in vitro antigens in all PBMC cultures.
RESULTS: Four subjects developed primary vaccination responses after initial vaccination. PBMC from 2 subjects had stimulation indices (SI=rgp160/rp24) greater than 4 (range 4.1-54.2; mean 20.6) and delta CPM(rgp160-rp24) greater than 4400(range 4415-14170; mean 9322) at days 28, 90 and 180, and alpha-IFN was detected in day 180 PBMC culture supernatants of one subject (titer=47u/ml). The subject examined longitudinally by LPA had SI of 1.4 and delta CPM=150 prior to initial vaccination and SI greater than 19 and delta CPM greater than 5500 at day greater than or equal to 28. The LPA results using PBMC from the other 3 subjects, one of whom did not develop a primary vaccination response, consistently had SI less than 2.0 and delta CPM less than 700. The 2 subjects with cellular responses were the only subjects who developed positive Western blots.
CONCLUSION: HIVAC-le induces HIV-1 rgp160-specific cellular immune responses in vaccinia-naive subjects following primary vaccination.
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1051
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