16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

ENHANCED HIV/SIV SPECIFIC CELLULAR IMMUNITY IN MACAQUES FOLLOWING A NOVEL PEPTIDE IMMUNOTHERAPY (OPAL)

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. ThAa0101

Kent S., Chea S., De Rose R., Batten C.J.
University of Melbourne, Microbiology and Immunology, Parkville, Australia

BACKGROUND: Preventing AIDS depends on manipulating effective immunity to HIV. We measured in vivo CTL responses in outbred macaques. During the development of these techniques we made a remarkable observation: the re-infusion of macaque blood pulsed with SIV/HIV peptides generated sharply enhanced SHIV-specific T cell immunity.

METHODS: For the in vivo CTL assay, PBMC from 6 pre-immune pigtail macaques, were incubated with pools of SIV Gag or SIV Pol overlapping 15mer peptides and labelled with fluorescent dyes. Autologous peptide-pulsed/labelled PBMC were re-infused into the macaques, and the stained cells tracked by FACS. T cell immunity following re-infusion of peptide-pulsed blood cells was evaluated by ICS in 24 macaques.

RESULTS: CTL lysis of Gag-pulsed cells was detected by 4 h post-infusion (up to 27.3%) in 4 pre-immune macaques, which subsequently increased to 76% by 16 h post-infusion. No lysis was observed in control-vaccinated macaques.

Strong, broad CD4+ and CD8+ T cell responses were simultaneously enhanced to all SHIV peptide pools used following infusion of peptide-pulsed PBMC. Up to 10% of all CD4, and 4% of CD8 T cells responded to SHIV antigens by ICS. We subsequently infused autologous whole blood pulsed with peptides spanning 87% of all SIV/HIV-1 proteins in an additional 11 pigtail macaques. New CD4 and CD8 T cell immune responses occurred to all infused SHIV peptide pools. Studies in 7 further macaques demonstrated new T cell responses to peptides spanning either ARV drug resistance mutations or all HCV proteins with this technique.

CONCLUSIONS: CTL responses can be monitored in vivo by infusing peptide-pulsed autologous cells. The infusion of Overlapping Peptide-pulsed Autologous cells (OPAL) sharply enhances broad SHIV-specific CD4+ and CD8+ T cell responses. This simple technique holds promise for the immunotherapy of HIV.

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2006-08-13
ThAa0101

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