Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed Blood

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Abstract
Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIVmac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably ∼10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans. Effective immunotherapies for HIV are needed. We assessed a simple technique, reinfusion of fresh blood cells incubating with overlapping SIV peptides (Overlapping Peptide-pulsed Autologous ceLls, OPAL), in 36 randomly allocated SIV-infected monkeys. We analyzed this therapy for the stimulation of immunity, control of virus levels, and prevention of AIDS. The OPAL immunotherapy was safe and stimulated remarkable levels of T-cell immunity. Levels of virus in vaccinated monkeys were 10-fold lower than in controls, and this was durable for over 1 year after the initial vaccinations. The immunotherapy resulted in fewer deaths from AIDS. We conclude this is a promising immunotherapy technique. Trials in HIV-infected humans of OPAL therapy are planned.