IMMUNOGENICITY OF RECOMBINANT VACCINIA VIRUS EXPRESSING ENV GLYCOPROTEINS: HIV

这个项目已于去年竣工。我们以前报道过，用表达SIVmne囊膜糖蛋白gp160的重组痘苗病毒免疫，然后用gp160蛋白加强免疫，可以在初治和免疫的猕猴中产生保护性免疫。在攻击后对动物进行长达5年的跟踪，以确定感染的临床结果和免疫的效果。E11S和未克隆的SIVmne病毒在丛枝杆菌中都显示出致病潜力。然而，感染非克隆病毒导致的病程比E11S更快。在感染未克隆病毒的动物中，与对照组相比，免疫动物的CD4细胞下降的开始时间明显延迟(免疫动物为95.0q15.4wk，对照组为41.0q12.3)。然而，在因艾滋病而需要安乐死的数量(2/10比5/10)以及感染艾滋病的动物的平均生存时间方面，免疫组和对照组之间没有显著差异。到目前为止，所有存活的动物病毒载量都很低，只有通过聚合酶链式反应分析才呈阳性，这与病毒载量减少与长期生存相关的概念一致。因此，在缺乏灭菌免疫的情况下，降低病毒载量可能是接种疫苗的理想终点。

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.