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用卡介苗或卡介苗加灭活麻风杆菌对恒河猴进行抗麻风保护性接种:免疫学观察

Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.

作者信息

Gormus B J, Baskin G B, Xu K, Ratterree M S, Martin L N, Mack P A, Bohm R P, Meyers W M, Walsh G P

机构信息

Department of Microbiology, Tulane Regional Primate Research Center, Covington, LA 70433, USA.

出版信息

Int J Lepr Other Mycobact Dis. 2000 Mar;68(1):27-39.

PMID:10834067
Abstract

Groups of rhesus monkeys were vaccinated and boosted with Mycobacterium bovis bacillus Calmette Guerin (BCG) or BCG plus low-dose (LD) or high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and following vaccination-boosting and subsequent M. leprae (ML) challenge, these and unvaccinated, unchallenged control monkeys were observed longitudinally for approximately 3 years. Vaccination with BCG plus HKML initially stimulated significant in vitro blood mononuclear cell blastogenic responses to lepromin, which returned to baseline post-boosting and post-live-ML-challenge, minimally reappearing significantly 2 years post-ML-challenge. Vaccination with BCG failed to stimulated positive blastogenic responses to lepromin before ML-challenge but small, marginally positive, intermittent responses were seen post-ML-challenge. Compared to the unvaccinated ML-challenged group, significant increases in the numbers of blood CD4+ and CD8+ T-cell subsets and an increased CD4+:CD8+ ratio were observed in both BCG plus HKML-vaccinated, ML-challenged groups, but not in the BCG-only-vaccinated, ML-challenged group. CD4+CD29+ and CD4+CD45RA+ subset numbers increased significantly over time in only the BCG plus LD HKML-vaccinated, ML-challenged group. Compared to unvaccinated, ML-challenged groups, vaccination with BCG or BCG plus HKML followed by ML-challenge produced lower IgM:IgG antiphenolic glycolipid-I (PGL-I) serum antibody ratios and protected rhesus monkeys from clinical leprosy, consistent with prior observations that low IgM:IgG anti-PGL-I responses correlated with resistance to and protection from leprosy.

摘要

将恒河猴分组,分别用卡介苗(BCG)、卡介苗加低剂量(LD)或高剂量(HD)热灭活麻风杆菌(HKML)进行接种和加强免疫,或不进行接种。在接种-加强免疫之前和之后以及随后进行麻风杆菌(ML)攻击之前和之后,对这些猴子以及未接种、未攻击的对照猴子进行了大约3年的纵向观察。用卡介苗加HKML进行接种最初刺激了体外血液单核细胞对麻风菌素的显著增殖反应,在加强免疫后和活ML攻击后恢复到基线水平,在ML攻击后2年时最低程度地再次显著出现。用卡介苗接种在ML攻击前未能刺激对麻风菌素的阳性增殖反应,但在ML攻击后可见小的、勉强为阳性的间歇性反应。与未接种ML攻击组相比,在卡介苗加HKML接种、ML攻击的两组中均观察到血液CD4+和CD8+ T细胞亚群数量显著增加以及CD4+:CD8+比值升高,但在仅接种卡介苗、ML攻击的组中未观察到。仅在卡介苗加LD HKML接种、ML攻击的组中,CD4+CD29+和CD4+CD45RA+亚群数量随时间显著增加。与未接种ML攻击组相比,用卡介苗或卡介苗加HKML接种后再进行ML攻击产生了较低的IgM:IgG抗酚糖脂-I(PGL-I)血清抗体比值,并保护恒河猴免受临床麻风病感染,这与先前的观察结果一致,即低IgM:IgG抗PGL-I反应与对麻风病的抵抗力和保护作用相关。

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