IMMUNOGENICITY OF RECOMBINANT VACCINIA VIRUS EXPRESSING ENV GLYCOPROTEINS: HIV

这个项目是去年完成的。 我们以前报道过，可以产生保护性免疫接种疫苗的幼稚以及疫苗免疫猕猴免疫表达SIVmne包膜糖蛋白gp 160的重组牛痘病毒，然后加强免疫gp 160蛋白。 在攻击后对动物进行长达5年的随访，以确定感染的临床结果和免疫的效果。 E11 S和未克隆的SIVmne病毒对M.束状肌然而，感染未克隆的病毒导致比E11 S更快的病程。 在感染未克隆病毒的动物中，与对照组相比，免疫组动物中CD 4细胞下降的开始时间显著延迟（免疫组动物为95.0q15.4周，对照组为41.0q12.3周）。 然而，免疫组和对照组动物因AIDS需要安乐死的数量（2/10 vs. 5/10）以及发生AIDS的动物的平均存活时间均无显著差异。 到目前为止，所有存活的动物都具有低病毒载量，并且仅通过PCR分析呈阳性，这与病毒载量降低与长期存活相关的概念一致。 因此，在缺乏杀菌免疫的情况下，病毒载量的降低可能是疫苗接种的理想终点。

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.