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Ag85B 联合 c-di-AMP 作为黏膜佐剂对小鼠持续性结核分枝杆菌感染具有免疫治疗作用。

Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice.

机构信息

College of Life Sciences, Northwest University, Xi'an, China.

Department of Microbiology and Pathogen Biology, Air Force Medical University, Xi'an, China.

出版信息

Braz J Med Biol Res. 2024 Jul 1;57:e13409. doi: 10.1590/1414-431X2024e13409. eCollection 2024.

DOI:10.1590/1414-431X2024e13409
PMID:38958367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11221865/
Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

摘要

结核病（TB）是由结核分枝杆菌引起的，仍然是世界上单一感染源导致死亡的主要原因。结核分枝杆菌感染也可能导致临床慢性感染，称为潜伏性结核感染（LTBI）。与目前有限的治疗方法相比，几种亚单位疫苗显示出免疫治疗效果，并被纳入临床试验。在这项研究中，一种新型粘膜佐剂 c-di-AMP 的 Ag85B 亚单位疫苗（Ag85B：c-di-AMP）通过鼻腔内给药，用于持续的结核分枝杆菌 H37Ra 感染小鼠模型，该模型也呈现出 LTBI 的无症状特征。与 Ag85B 免疫接种相比，Ag85B：c-di-AMP 疫苗接种诱导了更强的体液免疫应答，显著增加了 CD4+T 细胞募集，增强了肺部 Th1/Th2/Th17 表型应答，减少了肺部的病理损伤，并降低了小鼠中的结核分枝杆菌负荷。总之，Ag85B：c-di-AMP 粘膜途径免疫接种对持续的结核分枝杆菌 H37Ra 感染提供了免疫治疗效果，c-di-AMP 作为一种有前途的潜在粘膜佐剂，可进一步用于持续的结核分枝杆菌感染以及 LTBI 的治疗或预防性疫苗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/7719962aa1a2/1414-431X-bjmbr-57-e13409-gf006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/0702920a0803/1414-431X-bjmbr-57-e13409-gf001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/282e604cb736/1414-431X-bjmbr-57-e13409-gf002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/1b4b97961aff/1414-431X-bjmbr-57-e13409-gf003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/941eec84ae0f/1414-431X-bjmbr-57-e13409-gf004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/8271f9d6ecd8/1414-431X-bjmbr-57-e13409-gf005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/7719962aa1a2/1414-431X-bjmbr-57-e13409-gf006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/0702920a0803/1414-431X-bjmbr-57-e13409-gf001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/282e604cb736/1414-431X-bjmbr-57-e13409-gf002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/1b4b97961aff/1414-431X-bjmbr-57-e13409-gf003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/941eec84ae0f/1414-431X-bjmbr-57-e13409-gf004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/8271f9d6ecd8/1414-431X-bjmbr-57-e13409-gf005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9beb/11221865/7719962aa1a2/1414-431X-bjmbr-57-e13409-gf006.jpg

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