Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models.
Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models.
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亚单位疫苗在野生型和免疫受损小鼠模型中保护免受鸟分枝杆菌临床分离株的侵害。
DOI：
10.1038/s41598-021-88291-8
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发表时间：
2021-04-27
影响因子：
4.6
通讯作者：
Coler RN
中科院分区：
文献类型：
--
作者：
Larsen SE;Reese VA;Pecor T;Berube BJ;Cooper SK;Brewer G;Ordway D;Henao-Tamayo M;Podell BK;Baldwin SL;Coler RN
非结核分支杆菌（NTM）鸟分支杆菌是一种具有临床意义的病原体，可引起多种疾病，包括结核样肺病。免疫功能低下的宿主状态，无论是遗传性的还是急性获得性的，都存在进行性NTM感染的巨大风险。由于这种悄然出现的健康威胁，我们评估了重组融合蛋白ID 91与GLA-SE [吡喃葡萄糖基脂质佐剂，一种在水包油稳定的纳米乳剂中配制的toll样受体4激动剂]组合在C57 BL/6（野生型）和Beige（免疫受损）小鼠模型中赋予保护的能力。我们使用临床NTM分离株优化了气溶胶激发模型：M。avium 2-151 smt，观察细菌生长动力学、菌落形态、药物敏感性和组织病理学，表征肺免疫细胞的流入，并证实ID 91在两种小鼠模型中的免疫原性。为了确定预防性疫苗对该M.禽流感分离株，用ID 91 + GLA-SE或卡介苗（BCG）免疫小鼠。与C57 BL/6小鼠相比，免疫功能低下的米色小鼠显示先天性和适应性免疫细胞的延迟流入，导致肺和脾中持续和增加的细菌负荷。重要的是，ID 91 + GLA-SE和BCG疫苗均显著降低了两种小鼠品系中的肺部细菌负荷。这项工作是亚单位疫苗诱导的对NTM的保护的概念验证研究。
The nontuberculous mycobacteria (NTM) Mycobacterium avium is a clinically significant pathogen that can cause a wide range of maladies, including tuberculosis-like pulmonary disease. An immunocompromised host status, either genetically or acutely acquired, presents a large risk for progressive NTM infections. Due to this quietly emerging health threat, we evaluated the ability of a recombinant fusion protein ID91 combined with GLA-SE [glucopyranosyl lipid adjuvant, a toll like receptor 4 agonist formulated in an oil-in-water stable nano-emulsion] to confer protection in both C57BL/6 (wild type) and Beige (immunocompromised) mouse models. We optimized an aerosol challenge model using a clinical NTM isolate: M. avium 2-151 smt, observed bacterial growth kinetics, colony morphology, drug sensitivity and histopathology, characterized the influx of pulmonary immune cells, and confirmed the immunogenicity of ID91 in both mouse models. To determine prophylactic vaccine efficacy against this M. avium isolate, mice were immunized with either ID91 + GLA-SE or bacillus Calmette–Guérin (BCG). Immunocompromised Beige mice displayed a delayed influx of innate and adaptive immune cells resulting in a sustained and increased bacterial burden in the lungs and spleen compared to C57BL/6 mice. Importantly, both ID91 + GLA-SE and BCG vaccines significantly reduced pulmonary bacterial burden in both mouse strains. This work is a proof-of-concept study of subunit vaccine-induced protection against NTM.
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DOI：
10.1164/rccm.201807-1273pp
发表时间：
2019-04-15
影响因子：
24.7
作者：
Daniel-Wayman, Shelby;Abate, Getahun;Zelazny, Adrian M.
通讯作者：
Zelazny, Adrian M.
DOI：
10.1164/rccm.201205-0825oc
发表时间：
2012-10-01
影响因子：
24.7
作者：
Dirac, M. Ashworth;Horan, Kathleen L.;Cangelosi, Gerard A.
通讯作者：
Cangelosi, Gerard A.
影响因子：
6.4
作者：
Coler, Rhea N.;Bertholet, Sylvie;Reed, Steven G.
通讯作者：
Reed, Steven G.
影响因子：
7.3
作者：
Dhanda SK;Karosiene E;Edwards L;Grifoni A;Paul S;Andreatta M;Weiskopf D;Sidney J;Nielsen M;Peters B;Sette A
通讯作者：
Sette A
影响因子：
3.7
作者：
Amaral, Eduardo Pinheiro;Kipnis, Thereza Liberman;Lasunskaia, Elena B.
通讯作者：
Lasunskaia, Elena B.