EXPERIMENTAL LEPROSY & VACCINE STUDIES IN MONKEYS

实验性麻风病

• 批准号: 6247260
• 负责人: BOBBY J GORMUS
• 金额: $ 14.85万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-09 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247260
• 关键词: Mammalia; Primates; animal tissue; bacteria; communicable diseases; immunology; model design /development; nervous system; skin; vaccines

We continued to clinically monitor 3 groups of vaccinated [BCG or BCG + 2 doses of heat-killed M. leprae (HKML)] and one group of unvaccinated (control) rhesus monkeys (RM) and sooty mangabey monkeys (SMM) to determine long term clinical consequences of vaccination/live M. leprae challenge. There were 10 RM and 7 SMM per group. The clinical results were as follows 1) vaccination with BCG alone protected RM by 70%; 2) BCG + low dose (LD) or high dose (HD) HKML protected RM by 85%; 3) BCG vaccination significantly slowed the rate and the degree of leprosy progress in SMM, but failed to significantly diminish the total number of animals developing clinical symptoms long term (long-term protection by BCG alone would have probably been significant if there had been a larger number of SMM/group); and 4) BCG + LD or HD HKML vaccination exacerbated leprosy susceptibility in SMM. Since we have observed that RM tend (approx. 80%) to develop paucibacillary (PB) forms of leprosy and SMM develop (approx. 80%)multibacillary (MB) forms, the data suggest that BCG + HKML protect animals that have a predisposition towards susceptibility to PB forms of leprosy, but exacerbate susceptibility of animals with an innate predisposition towards MB forms of leprosy. BCG appears to protect very effectively at the PB end and less so at the MB end of the spectrum. A report from Vietnam agrees with our observations in that BCG + HKML only offered protection in geographic areas which had high percentages of PB-prone humans. Since it cannot be readily predicted which individuals are susceptible to PB vs. MB forms of leprosy, it is recommended that BCG + HKML not be utilized for vaccination of humans. BCG alone, on the other hand appears to be safe and effective over the entire range of leprosy types, especially so at the PB end of the spectrum. These observations help to explain the extreme variability (from 20-80%) in the protective rates of BCG vaccination against leprosy among various human populations (which vary in the proportions of PB:MB forms of leprosy). Our BCG results are in agreement with these reports of field trials among human populations.

我们继续在临床上监测3组接种疫苗[BCG或 BCG + 2剂量的热杀死M. Leprae（hkml）]和一组 未接种疫苗（对照）恒河猴（RM）和烟熏芒果猴子 （SMM）确定疫苗接种/LIVE的长期临床后果 M. Leprae挑战。 每组有10 rm和7 SMM。 这 临床结果如下1）单独使用BCG疫苗接种 保护RM 70％； 2）BCG +低剂量（LD）或高剂量（HD）hkml 保护RM 85％； 3）BCG疫苗接种大大减慢了速度 麻风病在SMM中的进展程度，但未能显着 减少长期产生临床症状的动物总数 术语（仅BCG的长期保护可能是 如果有更多的SMM/组）；和4） BCG + LD或HD HKML疫苗接种加剧了麻风病的敏感性 SMM。 由于我们已经观察到RM趋向于发展（约80％） 麻风病和SMM发展的paucibaCillary（PB）形式（大约。 80％）多账（MB）形式，数据表明BCG + HKML 保护对易感性易感性的动物 麻风病的Pb形式，但具有使动物的敏感性加剧了 对麻风病的MB形式的先天倾向。 BCG似乎 在PB端非常有效地保护，而在MB端则更少 频谱。 越南的报告同意我们的观察 BCG + HKML仅在具有的地理区域提供保护 PB容易发生的人数很高。 因为它不容易 预测哪些人容易受到PB与MB形式的影响 麻风病，建议不要将BCG + HKML用于 人类疫苗接种。 另一方面，单独的BCG似乎是 在整个麻风类型中，安全有效，尤其是 因此，在频谱的PB端。 这些观察有助于解释 BCG保护率的极端变异性（从20-80％） 在各种人群中针对麻风病的疫苗接种（这 与PB的比例不同：麻风病的MB形式）。 我们的BCG结果 与人类中的这些现场试验报告一致 人群。