ANTI TUBERCULOSIS CANDIDATE VACCINE TESTING IN RHESUS MONKEYS: MYCOBACTERIA

正常恒河猴(RM)被用一系列的 结核分枝杆菌浓度(1×102-6×106)， H37Rv菌株，确定最适攻毒剂量。Rm组 以前接种过疫苗，并用2剂培养滤液加强免疫 H37Rv蛋白(CFP)与QS-21佐剂或单独使用QS-21 然后用6 X 106 H37Rv MTB挑战，并被跟踪 临床上和免疫学上都是。在几个月的时间里，所有12个RM都显示出 临床或/和尸检时有结核病的证据。疾病 有些进展较快，而另一些进展相当缓慢 个体，但在统计上与 疫苗接种是可以辨别的。然而，每组只有4个RM， 只有明显的差异才能显示出 意义。体外纵向成纤维细胞反应 刀豆蛋白A、植物血凝素、结核菌素、CFP和结核分枝杆菌10kD 蛋白质与活H37Rv的挑战后没有显示出任何一致的 3组间差异有统计学意义。这些 结果与我们之前的研究一致，表明没有 在皮肤试验中有显著的原始细胞差异或差异 结果接种组与未接种组使用CFP或结核菌素效果比较 接种疫苗后或加强免疫后。数据显示，QS-21 佐剂本身具有免疫抑制作用；QS-21中高剂量CFP 倾向于克服压制。结果表明，QS-21是 不是用于灵长类动物的可接受的佐剂，并使 关于CFP作为一种保护措施的可能有效性的问题 疫苗与适当的佐剂相结合。滴定 确定rm相对致命性的研究正在进行中。 H37Rv和更具致病性的结核分枝杆菌Erdman株之间。在… 目前，没有

Normal rhesus monkeys (RM) were challenged with a range of concentrations (1 X 102-6 X 106) of Mycobacterium tuberculosis (MTB), strain H37Rv, to determine optimal challenge dose. Groups of RM previously vaccinated and boosted with 2 doses of culture-filtrate protein (CFP) from H37Rv together with QS-21 adjuvant or QS-21 alone were then challenged with 6 X 106 H37Rv MTB and were followed clinically and immunologically. Over several months, all 12 RM showed evidence of tuberculosis clinically or/and at necropsy. Disease progression was more rapid in some and quite slow in other individuals, but no statistically significant association with the vaccinations could be discerned. There were only 4 RM/group, however, and only clear-cut differences could be expected to have shown significance. Longitudinal in vitro blastogenesis responses to Concanavalin A, phytohemagglutinin, tuberculin, CFP and to MTB 10 Kd protein post-challenge with live H37Rv failed to show any consistent statistically significant differences between the 3 groups. These results were consistent with our prior studies that showed no significant blastogenic differences or differences in skin test results using CFP or tuberculin in vaccinated vs unvaccinated groups post-vaccination or post-boosting. The data indicated that the QS-21 adjuvant was itself immunosuppressive; higher doses of CFP in QS-21 tended to overcome the suppression. The results show that QS-21 is not an acceptable adjuvant for use in primates, and leaves open the question as to the possible effectiveness of CFP as a protective vaccine in combination with an appropriate adjuvant. Titration studies are in progress to determine the relative lethality in RM between the H37Rv and the more pathogenic Erdman strain of MTB. At present, there does not