De Rose Robert, Mason Rosemarie D, Loh Liyen, Peut Viv, Smith Miranda Z, Fernandez Caroline S, Alcantara Sheilajen, Amarasena Thakshila, Reece Jeanette, Seddiki Nabila, Kelleher Anthony D, Zaunders John, Kent Stephen J
Department of Microbiology and Immunology, University of Melbourne, Australia.
J Med Primatol. 2008 Dec;37 Suppl 2:69-78. doi: 10.1111/j.1600-0684.2008.00329.x.
Simple and effective delivery methods for cellular immunotherapies are needed. We recently published on the effectiveness of using ex vivo pulsing of overlapping SIV Gag 15mer peptides onto fresh peripheral blood cells in 32 SIV(mac251)-infected pigtail macaques.
We now report on the safety of this approach, analysis of a novel assay for immunogenicity, the effect of an MHC allele, Mane-A*10, on CD8 T cell escape occurring and disease outcome.
The vaccine strategy was safe, with no perturbations in weight or hematological profiles in comparison to controls. The high levels of SIV-specific T cell immunogenicity of this approach was confirmed using a novel assay measuring upregulation of surface CD134 of CD4 T cells. A substantial effect of the Mane-A10 allele in reducing SIV viral load of pigtail macaques was observed in both vaccinees and controls; the virologic efficacy of the immunotherapy in comparison to controls was greatest in Mane-A10- animals. Escape mutations at several new CD8 T cell epitopes throughout the SIV proteome were observed, primarily in animals with poorer virologic control.
In summary, we provide further information that peptide-pulsed PBMC are a safe, immunogenic and effective immunotherapy. The observed influence of MHC alleles and immune escape allows us to design more insightful future immunotherapy studies.
细胞免疫疗法需要简单有效的递送方法。我们最近发表了关于在32只感染SIV（mac251）的猪尾猕猴中，将重叠的SIV Gag 15聚体肽体外脉冲到新鲜外周血细胞上的有效性。
我们现在报告这种方法的安全性、一种新型免疫原性检测方法的分析、MHC等位基因Mane-A*10对CD8 T细胞逃逸发生及疾病结局的影响。
疫苗策略是安全的，与对照组相比，体重或血液学指标无异常。使用一种测量CD4 T细胞表面CD134上调的新型检测方法，证实了这种方法具有高水平的SIV特异性T细胞免疫原性。在疫苗接种组和对照组中均观察到Mane-A10等位基因对降低猪尾猕猴SIV病毒载量有显著作用；与对照组相比，免疫疗法在Mane-A10阴性动物中的病毒学疗效最佳。在整个SIV蛋白质组的几个新的CD8 T细胞表位观察到逃逸突变，主要发生在病毒学控制较差的动物中。
总之，我们提供了进一步的信息，即肽脉冲的PBMC是一种安全、具有免疫原性且有效的免疫疗法。观察到的MHC等位基因和免疫逃逸的影响使我们能够设计更具洞察力的未来免疫疗法研究。
