Klase Zachary, Donio Michael J, Blauvelt Andrew, Marx Preston A, Jeang Kuan-Teh, Smith Stephen M
Department of Infectious Diseases, Saint Michael's Medical Center, Newark, New Jersey, USA.
Retrovirology. 2006 Jan 6;3:1. doi: 10.1186/1742-4690-3-1.
CTL based vaccine strategies in the macaque model of AIDS have shown promise in slowing the progression to disease. However, rapid CTL escape viruses can emerge rendering such vaccination useless. We hypothesized that such escape is made more difficult if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins. To test this hypothesis, we immunized macaques using a peptide-loaded dendritic cell approach employing epitopes in the second coding exon of SIV Tat which spans reading frames for both Env and Rev. We report here that autologous dendritic cells, loaded with SIV peptides from Tat, Rev, and Env, induced a distinct cellular immune response measurable ex vivo. However, conclusive in vivo control of a challenge inoculation of SIVmac239 was not observed suggesting that CTL epitopes within densely overlapping reading frames are also subject to escape mutations.
在艾滋病猕猴模型中，基于细胞毒性T淋巴细胞（CTL）的疫苗策略已显示出减缓疾病进展的前景。然而，快速产生的CTL逃逸病毒会使此类疫苗接种变得无效。我们推测，如果免疫CTL表位位于病毒的一个区域内，该区域具有高密度的重叠阅读框，这些阅读框编码几种病毒蛋白，那么这种逃逸就会更加困难。为了验证这一假设，我们采用负载肽的树突状细胞方法免疫猕猴，该方法使用了SIV Tat第二个编码外显子中的表位，该外显子跨越Env和Rev的阅读框。我们在此报告，负载来自Tat、Rev和Env的SIV肽的自体树突状细胞在体外诱导了可测量的独特细胞免疫反应。然而，未观察到对SIVmac239攻击接种的体内决定性控制，这表明密集重叠阅读框内的CTL表位也容易发生逃逸突变。
