De Rose Robert, Fernandez Caroline S, Smith Miranda Z, Batten C Jane, Alcântara Sheilajen, Peut Vivienne, Rollman Erik, Loh Liyen, Mason Rosemarie D, Wilson Kim, Law Matthew G, Handley Amanda J, Kent Stephen J
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
PLoS Pathog. 2008 May 2;4(5):e1000055. doi: 10.1371/journal.ppat.1000055.
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 SIV(mac251) 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 approximately 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.
需要有效的HIV免疫疗法。药物疗法需要终身使用，且有显著的毒性。基于树突状细胞的免疫疗法很有前景，但不适合广泛应用。我们评估了一种简单的免疫疗法，即体外将新鲜的自体血细胞暴露于重叠的SIV肽1小时后再回输，用于控制36只猪尾猕猴体内SIV（mac251）的复制。在抗逆转录病毒药物的掩护下进行了最初的四次免疫接种，并在6个月后进行了三次加强免疫接种。将接种疫苗的动物随机分为单独接受Gag肽或接受涵盖所有九种SIV蛋白的肽。免疫接种后，无论是否在抗逆转录病毒药物掩护下，均诱导出了高水平的、SIV特异性的CD4和CD8 T细胞免疫。与对照组相比，免疫动物的病毒水平在1年内持续降低约10倍，并且艾滋病相关死亡率显著延迟。接种涵盖所有九种SIV蛋白的肽后产生了更广泛的免疫，但与仅接种Gag的动物相比，对Gag的反应较弱。与仅接种Gag的动物相比，接种所有SIV蛋白的动物在病毒结果方面没有差异。肽脉冲血细胞在感染SIV的猕猴中是一种具有免疫原性且有效的免疫疗法。我们的结果表明，单独的Gag是T细胞免疫疗法的有效抗原。用重叠Gag肽脉冲的新鲜血细胞正在进入HIV感染人类的试验。
