ANTI TUBERCULOSIS CANDIDATE VACCINE TESTING IN RHESUS MONKEYS: MYCOBACTERIA

恒河猴抗结核候选疫苗测试：分枝杆菌

• 批准号: 6277406
• 负责人: BOBBY J GORMUS
• 金额: $ 8.01万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277406
• 关键词: Mammalia; Primates; animal tissue; bacteria; immunology; infection; inflammation; model design /development; respiratory system; technology /technique; vaccines

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

正常的恒河猴（RM）受到一定范围的挑战 结核分枝杆菌（MTB）的浓度（1 x 102-6 x 106）， 菌株H37RV，以确定最佳挑战剂量。 RM组 以前已接种疫苗并用2剂培养物进行增强 H37RV的蛋白质（CFP）与QS-21佐剂或QS-21一起 然后用6 x 106 H37RV MTB挑战，然后遵循 在临床和免疫学上。 在几个月中，所有12 rm都显示 结核病的证据在临床上或/和尸检时。 疾病 某些进步速度更快，而其他方面的进展则很慢 个人，但与 可以辨别疫苗。 但是，只有4 rm/组 而且只有明确的差异可以显示 意义。 纵向的体外囊泡反应 康甘那藻A，植物凝血素，结核蛋白，CFP和MTB 10 kd 现场H37RV的促进后挑战后未能显示任何一致的 这三组之间的统计显着差异。 这些 结果与我们先前的研究一致，该研究表明 皮肤测试中的明显爆破性差异或差异 在接种疫苗中使用CFP或结核蛋白与未接种的组的结果 疫苗接种或促进后。 数据表明QS-21 佐剂本身就是免疫抑制。 QS-21中较高剂量的CFP 倾向于克服抑制。 结果表明QS-21是 在灵长类动物中不可接受的佐剂，叶子打开 关于CFP作为保护性的可能有效性的问题 疫苗与适当的佐剂结合使用。 滴定 正在进行研究以确定RM的相对致命性 在H37RV和MTB的病原性Erdman菌株之间。 在 在场，没有