Recombinant Mycobacterium smegmatis expressing antigen 85B for immunotherapy of Mycobacterium tuberculosis-infected mice

Hum Vaccin Immunother. 2025 Dec;21(1):2571287. doi: 10.1080/21645515.2025.2571287. Epub 2025 Oct 16.

Abstract

Tuberculosis is a serious, chronic infectious disease worldwide, primarily caused by Mycobacterium tuberculosis (Mtb). Antigen 85B is a potential vaccine candidate for Mtb. In this study, we constructed a recombinant strain expressing Antigen 85B (rMs-Ag85B) in the Mycobacterium smegmatis (Ms). The immunological characteristics and the therapeutic efficacy of the vaccine were evaluated in mice. The results showed that rMs-Ag85B exhibited slow growth under static culture conditions, with a significant reduction in biofilm formation compared to the Ms strain. Immunologically, subcutaneous immunization with rMs-Ag85B induced stronger humoral and cellular immune responses. As a therapeutic vaccine, rMs-Ag85B modulated the aggregation of CD4+ and CD8+ T cells in spleen and lung, promoted Th1/Th2-type cytokines secretions, and increased inflammatory cytokines releases and alleviated pathological damages in the lung of Mtb infected mice. Moreover, rMs-Ag85B significantly reduced the Mtb loads in the spleen of mice. In conclusion, rMs-Ag85B vaccine provided an immunotherapeutic effect against Mtb infection and could be used as a candidate vaccine for the immunotherapy of tuberculosis.

Keywords: Ag85B; Mycobacterium smegmatis; Mycobacterium tuberculosis; Tuberculosis; therapeutic vaccine.

MeSH terms

  • Acyltransferases* / genetics
  • Acyltransferases* / immunology
  • Animals
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial* / genetics
  • Antigens, Bacterial* / immunology
  • Bacterial Load
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Immunity, Cellular
  • Immunotherapy* / methods
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium smegmatis* / genetics
  • Mycobacterium smegmatis* / immunology
  • Mycobacterium tuberculosis / immunology
  • Spleen / immunology
  • Spleen / microbiology
  • Treatment Outcome
  • Tuberculosis Vaccines* / administration & dosage
  • Tuberculosis Vaccines* / genetics
  • Tuberculosis Vaccines* / immunology
  • Tuberculosis* / immunology
  • Tuberculosis* / prevention & control
  • Tuberculosis* / therapy
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antigens, Bacterial
  • Tuberculosis Vaccines
  • antigen 85B, Mycobacterium tuberculosis
  • Acyltransferases
  • Vaccines, Synthetic
  • Cytokines
  • Bacterial Proteins
  • Antibodies, Bacterial