Applications of bacillus Calmette–Guerin and recombinant bacillus Calmette–Guerin in vaccine development and tumor immunotherapy

Abstract

Summary Bacillus Calmette-Guerin (BCG) vaccines are attenuated live strains of Mycobacterium bovis and are among the most widely used vaccines in the world. BCG is proven effective in preventing severe infant meningitis and miliary tuberculosis. Intravesical instillation of BCG is also a standard treatment for non-muscle invasive bladder cancer. In the past few decades, recombinant BCG (rBCG) technology had been extensively applied to develop vaccine candidates against a variety of infectious diseases, including bacterial, viral, and parasite infections, and to improve the efficacy of BCG in bladder cancer therapy. This review is intended to show the vast applications of BCG and rBCG in prevention of infectious diseases and in cancer immunotherapy, with a special emphasis on recent approaches and trends on both pre-clinical and clinical levels.

Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches

“…A significant difference in time to first recurrence between BCG and chemotherapy was confirmed after follow‐up periods of greater than 8 years . However, there were no significant differences in disease progression and long‐term end points , although marginal differences for distant metastases ( p = 0.046), overall survival (OS; p = 0.023), and disease‐specific survival ( p = 0.026) comparing BCG and epirubicin chemotherapy were reported in a randomised phase III clinical trial with 837 patients . These studies also helped to optimise the dosage and schemes of BCG instillations .…”

Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases

“…Since then, many reports have been published refuting and supporting the causal relationship between TB and cancer both in animal studies and in humans. The studies included the circumstances where exposure to mycobacteria was via BCG vaccination instead of TB [4]. The use of BCG to treat stomach cancer was first reported in 1936 [90].…”

“…BCG is effective against other pathogenic mycobacteria: Mycobacterium avium, Mycobacterium leprae and Mycobacterium ulcerans; the infectious agents that respectively cause cervical lymphadenitis, leprosy and Buruli's ulcer [3]. BCG use is standard-of-care treatment for non-invasive bladder cancer; BCG as a bladder irrigant promotes an immune response that lessens the recurrence of bladder cancer [4].…”

Immunogenicity and protective efficacy of recombinant Bacille Calmette-Guerin strains expressing mycobacterium antigens Ag85A, CFP10, ESAT-6, GM-CSF and IL-12p70

“…By insertion of various immunostimulatory cytokines, recombinant BCG (rBCG) can be used as an effective modified vaccine to activate immune response and protect against severe forms of TB. 8,9 It has been reported, rBCG expressing PPE protein Rv3425 could induce Th1 immune response and provide long-term protection against TB by expanding lymphocytes, increasing IL-2 production and reducing IL-6 production 10 ; By overexpressing Ag85A, rBCG:Ag85A could induce stronger antigen-specific IFN-g response and higher antibody titer against H37Rv infection than BCG 11 ; rBCG strain expressing pro-apoptotic BAX was able to induce macrophages apoptosis, increase Ag85B-specific IgG2b/IgG1 ratio, promote IFN-g and IL-2 secretion, and reduce Ag85B-specific IL-4 content. 12 In addition, more and more studies began to put emphasis on combination use of immunostimulatory factors in establishment of rBCGs.…”