8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:50 (abstract no. 25)

K. J. Metzner¹, W. J. Moretto¹, S. M. Donahoe¹, M. Paluch², D. Schiller², F. V. Lee², A. Gettie¹, P. A. Marx³, J. P. Moore², D. D. Ho¹, J. Binley², D. F. Nixon¹, and R. I. Connor^1
1Aaron Diamond AIDS Res. Ctr. and Rockefeller Univ., New York, NY; ²Cornell Univ., New York, NY; and ³Tulane Univ. Med. Ctr., Covington, LA.

BACKGROUND: Previously, we have shown that in vivo depletion of CD8+ T cells resulted in a 1 to 2 log increase in replication of the live, attenuated vaccine strain SIVmac239 delta nef in immunized macaques. We now show that this transient viremia results in a significant boost in both SIV-specific T cell responses and anti-SIV antibodies. Strikingly, we also found that the early kinetics of this immune induction was highly predictive of subsequent protection from intravenous SIV challenge.

METHODS: Fourteen days after in vivo CD8+ T cell depletion, 2 of 6 macaques had a 1 to 2 log increase in anti-gp130 and -p27 antibody titers and a 3- to 5-fold increase in functional SIV gag- specific CD8+ T cells based on ELISPOT assays measuring IFN-γ secretion. Both macaques were protected from a pathogenic SIV challenge administered six months later. In contrast, the remaining 4 macaques were not protected from challenge and had only moderate increases in anti- gp130 and p27 antibodies and slow induction of functional SIV gag-specific T cells. In protected macaques, the rapid induction of SIV-specific CD8+ T cells was not associated with a significant increase in the release of naïve T cells from the thymus, suggesting expansion of a pre-existing memory population.

CONCLUSIONS: These results provide direct evidence that SIV-specific immunity can be significantly boosted by a transient burst of viremia in vivo. Importantly, the kinetics of induction of SIV-specific immune responses provides a critical, early parameter which is predictive of clinical outcome following exposure to pathogenic SIV.

2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.