Work

[Safety and humoral immune responses of an inactivated whole-cell lysate of Mycobacterium tuberculosis B/R fusion strain prepared by combined ultrasonic disruption and enzymatic digestion].

Year: 2026

Type: article

Abstract: OBJECTIVES: B/R fusion strain prepared by combined ultrasonic disruption and enzymatic digestion (UK-B/R) retains key antigenic components while ensuring complete bacterial inactivation; however, its safety and immunogenicity have not been fully characterized. This study aims to evaluate the safety of UK-B/R and the humoral immune responses induced by UK-B/R. METHODS: In the cell experiments, murine monocyte/macrophage leukemia RAW264.7 cells were divided into a blank control (control) group, a BCG group, a B/R group, and a UK-B/R group. After 24 h of treatment, the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA), and the apoptotic rate was determined by flow cytometry. In the animal experiments, 6-8-week-old C57BL/6J mice were randomly assigned to the phosphate-buffered saline (PBS), BCG, B/R, and UK-B/R groups for acute and long-term toxicity studies. In the acute toxicity study, mice in each group received a single subcutaneous administration and were observed continuously for 14 days. General condition, changes in body weight, mortality, and other parameters were recorded. In the long-term toxicity study, mice in each group were immunized subcutaneously on days 0, 14, and 28. Serum and lung, liver, spleen, and kidney tissues were collected on day 3 (acute phase) and day 14 (recovery phase) after the final immunization. Organ indices were calculated, and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), serum creatinine (SCr), and blood urea nitrogen (BUN) were measured. Hematoxylin and eosin staining was performed to assess histopathological changes in major organs. In addition, 15 female C57BL/6J mice aged 6 to 8 weeks were randomly assigned to the PBS, BCG, and UK-B/R groups. On day 14 after the final subcutaneous immunization, antigen-specific antibody levels in serum and bronchoalveolar lavage fluid (BALF) were measured by ELISA. RESULTS: <0.05). CONCLUSIONS: UK-B/R demonstrated favorable safety profiles at both the cellular and animal levels and induced antigen-specific humoral and mucosal immune responses.

Source: PubMed Central

DOI: 10.11817/j.issn.1672-7347.2026.260001