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

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-01 eCollection Date: 2024-01-01 DOI:10.1590/1414-431X2024e13409

Xuan Liang, Ruonan Cui, Xue Li, Huanhuan Ning, Jian Kang, Yanzhi Lu, Shan Zhou, Xinying Huang, Yujun Peng, Jingyao Zhang, Shiyun Li, Yanling Ma, Yinlan Bai

{"title":"Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice.","authors":"Xuan Liang, Ruonan Cui, Xue Li, Huanhuan Ning, Jian Kang, Yanzhi Lu, Shan Zhou, Xinying Huang, Yujun Peng, Jingyao Zhang, Shiyun Li, Yanling Ma, Yinlan Bai","doi":"10.1590/1414-431X2024e13409","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221865/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/1414-431X2024e13409","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

以 c-di-AMP 作为粘膜佐剂的 Ag85B 对小鼠持续性结核分枝杆菌感染有免疫治疗作用。

由结核分枝杆菌引起的结核病（TB）仍然是世界上单一传染病致死的主要原因。结核分枝杆菌感染也可能导致临床慢性感染，即所谓的潜伏结核感染（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。在本研究中，Ag85B亚单位疫苗与新型粘膜佐剂c-di-AMP（Ag85B:c-di-AMP）一起经鼻内注射给持久性结核杆菌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 疫苗接种能诱导更强的体液免疫反应，显著提高 CD4+ T 细胞的招募率，增强肺部 Th1/Th2/Th17 特征反应，减少肺部病理损伤，并降低小鼠的结核杆菌载量。综上所述，Ag85B:c-di-AMP粘膜途径免疫对H37Ra型结核杆菌的持续感染有免疫治疗作用，c-di-AMP作为一种有潜力的粘膜佐剂，可进一步用于结核杆菌持续感染和LTBI的治疗或预防性疫苗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.