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静脉接种卡介苗佐剂后产生的稳健 IgM 应答与猕猴预防结核分枝杆菌感染有关。

Robust IgM responses following intravenous vaccination with Bacille Calmette-Guérin associate with prevention of Mycobacterium tuberculosis infection in macaques.

机构信息

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

出版信息

Nat Immunol. 2021 Dec;22(12):1515-1523. doi: 10.1038/s41590-021-01066-1. Epub 2021 Nov 22.

DOI:10.1038/s41590-021-01066-1
PMID:34811542
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8642241/
Abstract

Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection against Mycobacterium tuberculosis (Mtb). Intravenous (i.v.) vaccination with Bacille Calmette-Guérin (BCG) provides nearly complete protection against TB in rhesus macaques, but the antibody response it elicits remains incompletely defined. Here we show that i.v. BCG drives superior antibody responses in the plasma and the lungs of rhesus macaques compared to traditional intradermal BCG administration. While i.v. BCG broadly expands antibody titers and functions, IgM titers in the plasma and lungs of immunized macaques are among the strongest markers of reduced bacterial burden. IgM was also enriched in macaques that received protective vaccination with an attenuated strain of Mtb. Finally, an Mtb-specific IgM monoclonal antibody reduced Mtb survival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and mediator of protection against TB.

摘要

开发有效的结核病（TB）疫苗一直受到对结核分枝杆菌（Mtb）保护相关因素认识不完整的阻碍。静脉内（i.v.）接种卡介苗（BCG）可使恒河猴几乎完全免受结核病的侵害，但它引起的抗体反应仍未完全确定。在这里，我们发现与传统的皮内 BCG 给药相比，i.v. BCG 可在恒河猴的血浆和肺部中引起更优的抗体反应。虽然 i.v. BCG 广泛增加了抗体滴度和功能，但免疫猴子的血浆和肺部中的 IgM 滴度是细菌负荷减少的最强标记物之一。在接受减毒 Mtb 株保护性疫苗接种的恒河猴中，IgM 也得到了富集。最后，一种 Mtb 特异性 IgM 单克隆抗体可减少 Mtb 在体外的存活。总之，这些数据突出了 IgM 反应作为 TB 保护的标记物和介导物的潜在重要性。

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