 |
Reduced viremia and delayed disease progression following immunotherapy of SIV with peptide pulsed blood
Presented by Robert De Rose, Australia.
De Rose R.1, Fernandez C.1, Smith M.1, Peut V.1, Batten C.J.1, Rollman E.1, Loh L.1, Alcantara S.1, Mason R.1, Law M.2, Handley A.3, Kent S.1
1University of Melbourne, Microbiology & Immunology, Parkville, Australia, 2University of New South Wales, National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia, 3OPAL Therapeutics, Melbourne, Australia
Objectives: Overlapping Peptide-pulsed Autologous Blood (OPAL) immunotherapy induces strong, broad T cell responses in pigtail macaques through re-infusion of autologous peripheral blood cells pulsed with overlapping sets of 15mer peptides spanning SIV and HIV proteins. We addressed if OPAL facilitates control of viremia in a SIVmac251 model.
Methods: 36 pigtail macaques were infected with SIVmac251 and received ARV therapy from Week 3-10. Animals were randomised to receive overlapping SIV Gag peptides only (OPAL-Gag), peptides from all 9 SIV proteins (OPAL-All) or control, at Weeks 4, 6, 8 and 10. T cell responses were measured by IFNg intracellular cytokine staining. ARV therapy was withdrawn at Week 10 and VL and CD4 T cells monitored for 26 weeks.
Results: Induction of high level SIV-specific T cell responses above controls was observed in both OPAL groups. Mean Gag-specific responses were higher for the focused, Gag only, immunotherapy compared with broad immunotherapy (2.9% vs 1.8% of CD4 and 0.5% vs 0.1% of CD8 above control responses). Mean Env, Pol and combined regulatory protein-specific CD4/CD8 responses were elevated in the OPAL-All group (2.5%/11.7%, 0.8%/0.3% and 1.5%/2.9%, respectively) compared to <0.4% for all CD4/8 responses in the controls and OPAL-Gag groups. VL rebound post-ARV therapy was significantly reduced (mean 0.93 log10copies/mL) in OPAL immunised groups compared to controls (p=0.01 for mean time-weighted analysis) 6 months after ARV cessation. No difference was observed between OPAL groups. Evidence of progressive SIV infection was observed in 60% of controls compared to 6% of OPAL immunised animals. OPAL was well tolerated with no observed side effects.
Conclusions: OPAL immunotherapy induced elevated SIV-specific T cell responses in SIV infected macaques, reduced VL post-ARV therapy and delayed disease progression. T cell responses focused to Gag were as effective as broader responses. This technology holds promise for immunotherapy of HIV and other chronic viral infections.
Back to the session -
Back to the Programme-at-a-Glance
|
|