Mycobacterium bovis (BCG vaccine)

Mycobacterium bovis is a gram-positive, rod-shaped bacterium with anti-oxidant characteristics living in aerobic environment. It infects humans and cattle causing bovine tuberculosis^​1​. Technically, the scientific name for M. bovis is M. tuberculosis as this species turned out to be a later heterotypic synonym of Mycobacterium tuberculosis ^​2,3​. However, the name M. bovis, will be used in this writing for the recognition of the strain that has been used as the source of the BCG (Bacillus Calmette-Guerin) vaccine.  In 1997, the M. bovis genome was identified using the AF2122/97 strain isolated from an infected cow suffering from lung pain in the UK^​4​. The genome size was 4,345,492 bp in length and consisted of one circular chromosome with the GC ratio being 65.63%. 3,952 protein genes are included in the genome and have been found to be more than 99.95% identical to M. tuberculosis. 

In the early 1900s, there was an attempt to mitigate the toxicity of M. bovis isolated from cows by Albert Calmette and Camille Guerin in the Pasteur Institute in France. The strain was sub-cultured about 230 times for 11 years and as a result, the BCG vaccination was created^​5​​​. The first record of the inoculation of BCG vaccine to humans was made at the Charité Hospital in Paris in 1921. The safety and efficacy of the BCG vaccine were tested and proved. Since then the use of the BCG vaccine has gradually increased. Until the late 1940s, several studies had proved the evidence of BCG’s effectiveness in preventing tuberculosis. After World War II, the BCG vaccination was actively promoted by UNICEF, WHO, and the Scandinavian Red Cross, and additionally has spread to developing countries.

In the 1950s, two major clinical trials were conducted by the Medical Research Council in the United Kingdom and by the Public Health Service in the United States. While the tuberculin tests based on 13 years old youths (strain “Copenhagen” was used in the UK) was highly effective, the procedure performed in the United States (based on the strain “Tice”, given to various ages) only showed no or a little effect. After these trials, it was encouraged for youth to receive the BCG vaccination in the UK, whereas BCG was not recommended in the United States and was restricted to certain high-risk groups. Most countries in the world followed the lead of Europe and WHO, and BCG vaccination was widely adopted, except in two countries, the US and the Netherlands.

Although the BCG vaccine is extensively used, its effectiveness remains controversial. Due to two different results of the effectiveness of BCG from clinical trials in the UK and US, another large clinical trial has been conducted in the Chingleput region of South India starting in 1968. Two different BCG strains (Paris/Pasteur versus Danish) were chosen for comparative study in the Chingleput area known as a high-risk exposure with mycobacteria. The result was revealed in 1979, and surprisingly, it was found that the BCG vaccine had no preventive effects against pulmonary tuberculosis​^​6​​. However, various studies to evaluate the use of BCG have continued^​7,8​​, and most studies reported that it has some degree of preventive effect, although there is still no universally agreed-upon acceptance in using BCG. In any case, the BCG vaccine is still the only vaccine used to prevent tuberculosis in humans which prevents numerous deaths from tuberculosis each year. The only issue is which BCG strain to be used for vaccination.

Interestingly, the vaccination received an attention through a recently published research article^​9​ about the correlation between BCG and COVID-19. The New York Institute of Technology (NYIT) biomedical researchers report that BCG vaccination reduces the mortality from COVID-19 infection. They showed a statistical analysis that the prevalence and mortality of COVID-19 is significantly different between countries with and without routine BCG vaccination. Although WHO has not officially announced the evidence of BCG in preventing COVID-19, a clinical trial is being conducted to confirm the direct causal relationship is ongoing and will be evaluated after the results are released^​10​. We look forward to seeing the BCG to become a clue in solving the threatening disease in humankind once again.