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静脉注射卡介苗疫苗可预防感染猴免疫缺陷病毒的猕猴患结核病。

Intravenous Bacille Calmette-Guérin vaccination protects simian immunodeficiency virus-infected macaques from tuberculosis.

机构信息

Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Nat Microbiol. 2023 Nov;8(11):2080-2092. doi: 10.1038/s41564-023-01503-x. Epub 2023 Oct 9.

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the most common cause of death in people living with human immunodeficiency virus (HIV). Intra-dermal Bacille Calmette-Guérin (BCG) delivery is the only licensed vaccine against tuberculosis; however, it offers little protection from pulmonary tuberculosis in adults and is contraindicated in people living with HIV. Intravenous BCG confers protection against Mtb infection in rhesus macaques; we hypothesized that it might prevent tuberculosis in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. Here intravenous BCG-elicited robust airway T cell influx and elevated plasma and airway antibody titres in both SIV-infected and naive animals. Following Mtb challenge, all 7 vaccinated SIV-naive and 9 out of 12 vaccinated SIV-infected animals were protected, without any culturable bacteria detected from tissues. Peripheral blood mononuclear cell responses post-challenge indicated early clearance of Mtb in vaccinated animals, regardless of SIV infection. These data support that intravenous BCG is immunogenic and efficacious in SIV-infected animals.

摘要

结核分枝杆菌(Mtb)引起的结核病是导致人类免疫缺陷病毒(HIV)感染者死亡的最常见原因。皮内注射卡介苗(BCG)是唯一获准用于预防结核病的疫苗;然而,它对成人肺结核的保护作用有限,且对 HIV 感染者禁用。静脉内 BCG 可预防猕猴感染结核分枝杆菌;我们假设它可能预防感染猴免疫缺陷病毒(SIV)的猕猴发生结核病,SIV 感染的猕猴是 HIV 感染的模型。在此,静脉内 BCG 引起的气道 T 细胞大量涌入以及 SIV 感染和未感染动物的血浆和气道抗体滴度升高。在结核分枝杆菌感染后,所有 7 只接种疫苗的 SIV 未感染动物和 12 只接种疫苗的 SIV 感染动物均得到保护,未从组织中检测到可培养的细菌。感染后外周血单个核细胞的反应表明,无论 SIV 是否感染,接种疫苗的动物均能早期清除 Mtb。这些数据支持静脉内 BCG 在 SIV 感染的动物中具有免疫原性和有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/942b/10627825/d252e0d3f933/41564_2023_1503_Fig1_HTML.jpg

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