Evaluation of early innate and adaptive immune responses to the TB vaccine Mycobacterium bovis BCG and vaccine candidate BCGΔBCG1419c.
Evaluation of early innate and adaptive immune responses to the TB vaccine Mycobacterium bovis BCG and vaccine candidate BCGΔBCG1419c.
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DOI：
10.1038/s41598-022-14935-y
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发表时间：
2022-07-20
影响因子：
4.6
通讯作者：
Robinson, Richard T.
中科院分区：
文献类型：
--
作者：
Gunasena, Manuja;Shukla, Rajni Kant;Yao, Naiquan;Mejia, Oscar Rosas;Powell, Michael D.;Oestreich, Kenneth J.;de Jesus Aceves-Sanchez, Michel;Alberto Flores-Valdez, Mario;Liyanage, Namal P. M.;Robinson, Richard T.
牛分枝杆菌卡介苗 (BCG) 疫苗可引发免疫反应，从而预防某些形式的结核病 (TB)；然而，由于卡介苗的功效有限，因此确定替代结核病候选疫苗非常重要。最近，BCG 缺失突变体和候选疫苗 BCGΔBCG1419c 被证明由于生物膜形成增强，在静脉感染的 BALB/c 小鼠中存活时间更长，并且相对于 BCG 对照，在感染的慢性阶段更好地保护 BALB/c 和 C57BL/6 小鼠免受结核病引起的肺部病变。 BCGΔBCG1419c 引起的保护还与 C57BL/6 小鼠感染部位促炎细胞因子（即 IL6、TNFα）水平较低相关。鉴于慢性结核病期间接受 BCG 和 BCGΔBCG1419c 免疫的小鼠具有不同的免疫特征，我们着手在免疫后不久对肺部和其他组织进行多维流式细胞术分析，以确定是否存在区分这两组的早期免疫事件。我们的结果表明，BCG 免疫小鼠和 BCGΔBCG1419c 免疫小鼠之间存在许多先天性和适应性反应差异，这与后者持续时间更长且炎症可能更少相一致，包括耗尽的 CD4+ T 辅助 (TH) 细胞频率较低和产生 IL10 的 T 细胞频率较高。这些研究表明，使用 BCGΔBCG1419c 作为替代结核病候选疫苗可能是有利的。
The vaccine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) elicits an immune response that is protective against certain forms of tuberculosis (TB); however, because BCG efficacy is limited it is important to identify alternative TB vaccine candidates. Recently, the BCG deletion mutant and vaccine candidate BCGΔBCG1419c was demonstrated to survive longer in intravenously infected BALB/c mice due to enhanced biofilm formation, and better protected both BALB/c and C57BL/6 mice against TB-induced lung pathology during chronic stages of infection, relative to BCG controls. BCGΔBCG1419c-elicited protection also associated with lower levels of proinflammatory cytokines (i.e. IL6, TNFα) at the site of infection in C57BL/6 mice. Given the distinct immune profiles of BCG- and BCGΔBCG1419c-immunized mice during chronic TB, we set out to determine if there are early immunological events which distinguish these two groups, using multi-dimensional flow cytometric analysis of the lungs and other tissues soon after immunization. Our results demonstrate a number of innate and adaptive response differences between BCG- and BCGΔBCG1419c-immunized mice which are consistent with the latter being longer lasting and potentially less inflammatory, including lower frequencies of exhausted CD4+ T helper (TH) cells and higher frequencies of IL10-producing T cells, respectively. These studies suggest the use of BCGΔBCG1419c may be advantageous as an alternative TB vaccine candidate.
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DOI：
10.4049/jimmunol.1601231
发表时间：
2017-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cheekatla SS;Tripathi D;Venkatasubramanian S;Paidipally P;Welch E;Tvinnereim AR;Nurieva R;Vankayalapati R
通讯作者：
Vankayalapati R
影响因子：
3.3
作者：
Ackart DF;Hascall-Dove L;Caceres SM;Kirk NM;Podell BK;Melander C;Orme IM;Leid JG;Nick JA;Basaraba RJ
通讯作者：
Basaraba RJ
影响因子：
6.4
作者：
Faulkner, L;Buchan, G;Baird, M
通讯作者：
Baird, M
影响因子：
6.4
作者：
Guinn KM;Rubin EJ
通讯作者：
Rubin EJ
影响因子：
4.6
作者：
Alberto Flores-Valdez, Mario;de Jesus Aceves-Sanchez, Michel;Waters, Christopher M.
通讯作者：
Waters, Christopher M.