More vaccine efficacy studies on the recombinant Bacille Calmette-Guerin co-expressing Ag85B, Mpt64 and Mtb8.4.

The immunogenicity of the recombinant Bacille Calmette-Guerin: rBCG-Ag85B-Mpt64(190-198)-Mtb8.4 (rBCG-AMM) was evaluated in our previous study. This paper compares the protective efficacy of rBCG-AMM, rBCG-A which overexpresses Ag85B and BCG in C57BL/6 mice. There was no significant difference in proliferation characteristics among rBCG-AMM, rBCG-A and BCG. The growth characteristics of rBCG-AMM in host tissue were identical to control BCG, suggesting the improved protective efficacy was directly related to the expression of the Ag85B-Mpt64(190-198)-Mtb8.4 fusion protein. The protective experiment demonstrated that rBCG-AMM could confer similar or even better protective efficacy against Mycobacterium tuberculosis infection compared with BCG or rBCG-A as evaluated by bacterial organ loads, lung histopathology and net weight gain or loss. The results suggested that the recombinant BCG: rBCG-Ag85B-Mpt64(190-198)-Mtb8.4 is a potential vaccine candidate for further study.

Evaluation of a new recombinant BCG which contains mycobacterial antigen ag85B-mpt64(190-198)-mtb8.4 in C57/BL6 mice.

Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be one of the major public health problems in the world. The eventual control of this disease will require the development of a safe and effective vaccine. Bacille Calmette-Guerin (BCG), the only vaccine against TB, is not perfect for its limited ability to protect against the adult form of TB. Some improvements of TB vaccines relied to strengthening the immunogenicity and/or persistence of genetically modified recombinant BCG (rBCG) strain. Antigen 85B (Ag85B) and Mtb8.4 are importantly immunodominant antigens of M. tuberculosis, and both are very promising vaccine candidate molecules. MPT64(190-198), is presented to CD8(+) T cells during mycobacterial infections. In this study, we combined these above genes into one recombinant gene of ag85B-mpt64(190-198)-mtb8.4. Then we constructed the new rBCG containing this united gene. This rBCG can induce an increased Th1-type immune response in mice, characterized by an elevated level of interferon-gamma in antigen-stimulated splenocyte culture and a strong IgG2a antibody response. Also, it can elicit longer immune responses than BCG. The results show that this rBCG is a promising candidate for further study.