Enhanced Immune Responses Against Mycobacterium tuberculosis Through Heat-Killed BCG with Squalene-in-water Emulsion Adjuvant

Chuanzhi Zhu; Qingde Song; Xinrong Li; Xiuyun He; Junli Li

doi:10.1007/s12088-024-01278-7

Enhanced Immune Responses Against Mycobacterium tuberculosis Through Heat-Killed BCG with Squalene-in-water Emulsion Adjuvant

Indian J Microbiol. 2024 Dec;64(4):1929-1937. doi: 10.1007/s12088-024-01278-7. Epub 2024 May 27.

Authors

Chuanzhi Zhu¹, Qingde Song², Xinrong Li^{2

3}, Xiuyun He², Junli Li^{2

4}

Affiliations

¹ Laboratory of Molecular Biology, Beijing Key Laboratory for Drug Resistance Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149 China.
² Beijing Key Laboratory of Organ Transplantation and Immunology Regulation, The Eighth Medical Centre, Chinese PLA General Hospital, Beijing, 100091 China.
³ Clinical Laboratory, Guangzhou Development District Hospital, Chinese Association of Medicinal Biotechnology Southern Center of Biology Diagnosis and Therapy, Guangzhou, 510730 China.
⁴ Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing, 102629 China.

Abstract

The increasing challenge of drug-resistant tuberculosis (TB) calls for the development of innovative therapeutic strategies, highlighting the potential of adjunctive immunotherapies that are both cost-effective and safe. Host-directed therapy (HDT) using immunomodulators shows promise in enhancing treatment efficacy by modulating immune responses, thereby shortening the duration of therapy and reducing drug resistance risks. This study investigated the immunomodulatory potential of combining Heat-killed Bacillus Calmette-Guérin (hBCG) with a Squalene-based oil-in-Water Emulsion (SWE) adjuvant against TB. The therapeutic efficacy of the hBCG-SWE regimen was assessed in a guinea pig model infected with Mycobacterium tuberculosis (M. tb). Furthermore, the impact of hBCG-SWE on TNF-α and MCP-1 production was evaluated in RAW264.7 macrophages, examining the role of TLR2/4 and MyD88 signaling pathways using ELISA, both with and without specific inhibitors. Our findings revealed that hBCG-SWE significantly enhanced TNF-α and MCP-1 production compared to hBCG alone, indicating activation through TLR2/4 and MyD88-dependent pathways. In guinea pigs, hBCG-SWE administration led to notable reductions in lung pathology and spleen bacterial loads versus control groups. These results highlight the capacity of hBCG-SWE to boost innate immunity and provide robust protection against M. tb. Future research should focus on evaluating the ability of hBCG-SWE to shorten conventional chemotherapy and exploring ways to amplify its immunomodulatory efficacy through advanced formulation techniques.

Keywords: Heat-killed BCG; Immune responses; Immunomodulator; Mycobacterium tuberculosis; Squalene-in-Water Emulsion.

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