Expanded scope of Bacillus Calmette-Guerin (BCG) vaccine applicability in disease prophylaxis, diagnostics and immunotherapeutics

Following the discovery of the Bacillus Calmette-Guerin (BCG) vaccine, its efficacy against Mycobacterium tuberculosis was soon established, with several countries adopting universal BCG vaccination schemes for their populations. Soon, however, studies aimed to further establish the efficacy of the vaccine in different populations discovered that the vaccine has a larger effect in reducing mortality rate than could be explained by its effect on tuberculosis alone, which sparked suggestions that the BCG vaccine could have effects on other unrelated or non-mycobacterial pathogens causing diseases in humans. These effects were termed heterologous, non-specific or off-target effects and have been shown to be due to both innate and adaptive immune system responses. Experiments carried out in a bid to further understand these effects led to many more discoveries about the applicability of the BCG vaccine for the prevention, diagnosis, and treatment of certain disease conditions. As we approach the second century since the discovery of the vaccine, we believe it is timely to review these interesting applications of the BCG vaccine, such as in the prevention of diabetes, atherosclerosis, and leukemia; the diagnosis of Kawasaki disease; and the treatment of multiple sclerosis, non-muscle invading bladder cancer, and stage III melanoma. Furthermore, complications associated with the administration of the BCG vaccine to certain groups of patients, including those with severe combined immunodeficiency and HIV, have been well described in literature, and we conclude by describing the mechanisms behind these complications and discuss their implications on vaccination strategies, especially in low-resource settings.