[MoOrA1090] Direct demonstration of in vivo killing of HIV-labeled cells in macaques following DNA prime and Fowlpoxvirus boost HIV vaccines

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Direct demonstration of in vivo killing of HIV-labeled cells in macaques following DNA prime and Fowlpoxvirus boost HIV vaccines

[AUTHOR(S):] S.J. Kent, C.J. Dale, R. De Rose¹, C.J. Medveczky, I.A. Ramshaw²

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1090

BACKGROUND: Detection of HIV-specific T cell immunity induced by vaccines has been, up to date, at best indirect. We studied the direct killing of HIV labeled cells in vivo tracking dye-labeled cells in macaques receiving highly T cell immunogenic vaccines.

METHODS: Macaques were vaccinated consecutively with DNA and Fowlpoxvirus HIV-1 vaccines as previously reported (Kent et al J Virol 1998). 107 fresh autologous PBMC were first labeled with the vital dye SNARF and then pulsed with overlapping 15mer HIV-1gag peptides. Together with an equal number of non-peptide pulsed CSFE dye-labeled control PBMC, the SNARF-labeled HIV pulsed PBMC were infused into macaques the same day and followed in blood and lymph nodes over 1 week.

RESULTS: SNARF and CFSE-labeled macaque PBMC and lymph node cells could be readily recovered in control experiments for at least 1 week following infusion. In excess of 50% of the HIV-pulsed SNARF-labeled cells were killed, both in blood and lymph nodes, within 1-2 days of infusion in DNA/FPV immunized animals in comparison to non-HIV pulsed CFSE-labeled cells. Control macaques not receiving peptide pulsed cells did not have significant loss of SNARF-labeled cells and macaques previously infected with non-pathogenic HIV-1 demonstrated less in vivo killing of HIV-pulsed SNARF-labeled cells in comparison to DNA/FPV vaccinated macaques.

CONCLUSIONS: This is the first demonstration of the direct in vivo killing, both in blood and lymph nodes, of HIV labeled cells in primates. The data dramatically illustrate the high T cell immunity induced by DNA/FPV prime/boost HIV-1 vaccines in primates. DNA and FPV vaccine regimens should be readily capable of facilitating clearance of HIV-1 infected cells in humans exposed to HIV-1.

Presenting author: Stephen Kent

1University of Melbourne, Dept. of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia.

2Australian National University, Canberra, Australia.

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