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

• Published in: Brazilian journal of medical and biological research 2024-01, Vol.57, p.e13409
• Main Authors: Liang, Xuan, Cui, Ruonan, Li, Xue, Ning, Huanhuan, Kang, Jian, Lu, Yanzhi, Zhou, Shan, Huang, Xinying, Peng, Yujun, Zhang, Jingyao, Li, Shiyun, Ma, Yanling, Bai, Yinlan
• Format: Article
• Language: English
• Subjects: Acyltransferases - immunology; Adenylic acid; Adjuvant; Adjuvants; Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; Ag85B; AMP; Animals; Antigens, Bacterial - immunology; B cells; Bacterial Proteins - immunology; BCG; BCG vaccines; BIOLOGY; C-di-AMP; Care and treatment; CD4 antigen; Chronic infection; Clinical trials; Comparative analysis; Disease Models, Animal; Female; Helper cells; Immune response; Immune response (humoral); Immunization; Immunotherapy; Infections; Latent Tuberculosis - immunology; Lymphocytes T; Medical research; Medicine, Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Methods; Mice; Mice, Inbred BALB C; Mucosa; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Persistent infection; T cells; Testing; Tuberculosis; Tuberculosis - immunology; Tuberculosis - prevention & control; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - immunology; Vaccination; Vaccines; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; Viral proteins
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431X2024e13409

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.