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

Abstract

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 to be 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 for 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 recombinant BCG (rBCG) in the prevention of infectious diseases and cancer immunotherapy, with a special emphasis on recent approaches and trends on both pre-clinical and clinical levels.

Keywords:

• bacterial vector
• Bacillus Calmette-Guerin
• bladder cancer
• clinical applications
• infectious disease
• recombinant BCG
• tumor
• vaccine development

Financial & competing interests disclosure

Z Cui is supported by grants from the US National Institutes of Health (CA135274, AI105789, AI078304), the National Natural Science Foundation of China (81460454) and Inner Mongolia Natural Science Funds (2014ZD05). Y-C Shi is supported by the National “Twelfth Five-Year” Plan for Science & Technology Support of China (2014BAI13B03), the National Natural Science Foundation of China (81460248 and 81260457), Inner Mongolia Natural Science Funds (2013MS1138, 2012MS1121, and 2011MS1110) and Inner Mongolia Science & Technology Plan (20120101, 20120402, and 20110501). YW Naguib is the recipient of a doctoral scholarship from the Egyptian Ministry of Higher Education. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Bacillus Calmette–Guerin (BCG) vaccine is one of the most widely used vaccines in the world. BCG vaccine is one of the first oral vaccines.

• BCG vaccine is effective against infant meningitis and miliary tuberculosis, but not reliable against tuberculosis in adults.

• Intravesical instillation of BCG after transurethral resection is a standard bladder cancer therapy.

• BCG had been used as a bacterial vector to develop vaccine candidates against numerous pathogens and tumors.

• Heterologous priming and boosting regimen with a recombinant BCG vaccine is proven to be effective in eliciting strong CD8⁺ T cell immune responses, but priming and boosting with different vaccines should not be the first choice in vaccine development.

• Recombinant BCG vaccine candidates can induce both humoral and cellular immunity. They can also induce both systemic and mucosal immunity, if given via a proper mucosal route.

• To improve the effectiveness of BCG in bladder cancer therapy, and to enable the use of BCG in the therapy of other cancers, innovative strategies to increase the delivery and targeting of BCG into tumor cells are needed.