Safety, immunogenicity and efficacy of peptide-pulsed cellular immunotherapy in macaques
Safety, immunogenicity and efficacy of peptide-pulsed cellular immunotherapy in macaques
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DOI：
10.1111/j.1600-0684.2008.00329.x
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发表时间：
2008-12-01
影响因子：
0.7
通讯作者：
Kent, Stephen J.
中科院分区：
文献类型：
--
作者：
De Rose, Robert;Mason, Rosemarie D.;Kent, Stephen J.
需要用于细胞免疫疗法的简单且有效的递送方法。我们最近发表了关于在32只SIVmac 251感染的猪尾猕猴中使用重叠的SIV Gag 15 mer肽到新鲜外周血细胞上的体外脉冲的有效性。我们现在报告这种方法的安全性，分析免疫原性的新测定，MHC等位基因Mane-A*10对CD 8 T细胞逃逸发生和疾病结果的影响。疫苗策略是安全的，与对照组相比，体重或血液学特征没有变化。该方法的高水平SIV特异性T细胞免疫原性使用测量CD 4 T细胞的表面CD 134的上调的新测定法来证实。在接种者和对照组中均观察到Mane-A*10等位基因在降低猪尾猕猴SIV病毒载量方面的显著作用;与对照组相比，免疫治疗的病毒学功效在Mane-A*10动物中最大。逃逸突变在几个新的CD 8 T细胞表位在整个SIV蛋白质组中观察到，主要是在动物较差的virologiccontrol.In总结，我们提供了进一步的信息，肽脉冲PBMC是一种安全的，免疫原性和有效的免疫疗法。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有见地的未来免疫治疗研究。
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 SIVmac251-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-A*10 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-A*10- 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.