IMMUNOGENICITY OF RECOMBINANT VACCINIA VIRUS EXPRESSING ENV GLYCOPROTEINS: HIV

这个项目已于去年竣工。我们之前报道过， 保护性免疫可以在幼稚的牛痘中产生 重组牛痘免疫猕猴的研究 表达SIVmne包膜糖蛋白gp160的病毒，随后是 用gp160蛋白加强免疫。动物们被跟踪到 挑战后长达5年，以确定临床结果 感染和免疫的效果。E11S和未克隆 SIVmne病毒在丛枝杆菌中表现出致病潜能。然而， 感染非克隆病毒会导致一种更迅速的疾病 当然比E11S要好。在感染非克隆病毒的动物中， CD_4细胞下降的开始时间明显延迟 免疫动物与对照组的比较(95.0q15.4wk 免疫的动物与对照组的41.0q12.3)。然而，有一种 免疫组与对照组之间无显著差异 因艾滋病而需要安乐死的动物数量(2/10比 5/10)，也不是艾滋病患者的平均生存时间。所以 到目前为止，所有幸存的动物病毒载量都很低，只有阳性 通过聚合酶链式反应分析，与减少病毒载量的概念一致 与长期生存相关。因此，在没有 杀菌免疫，减少病毒载量可能是可取的 疫苗接种的终点。

This project was concluded last year. We previously reported that protective immunity can be generated in vaccinia-naive as well as vaccinia-immune macaques by immunization with recombinant vaccinia virus expressing SIVmne envelope glycoprotein gp160, followed by booster immunizations with gp160 protein. Animals were followed for up to 5 years after challenge to determine the clinical outcome of infection and the effects of immunization. Both E11S and uncloned SIVmne virus showed pathogenic potential in M. fascicularis. However, infection with the uncloned virus resulted in a more rapid disease course than E11S. Among animals infected with the uncloned virus, there was a significant delay of the onset of CD4 cell decline in immunized animals compared with the controls (95.0q15.4 wk for the immunized animals vs. 41.0q12.3 for the controls). However, there was no significant difference between the immunized and the control animals in the number that required euthanasia due to AIDS (2/10 vs. 5/10), nor the mean survival time among those that developed AIDS. So far, all surviving animals have low viral load and are positive only by PCR analysis, consistent with the notion that reduced viral load correlates with long-term survival. Therefore, in the absence of sterilizing immunity, reduction of viral load may be a desirable endpoint for vaccination.