100 years of BCG vaccine

In July 1921, a French baby became the first person to receive an vaccine against tuberculosis after his mother died of tuberculosis. The vaccine known as Bacille Calmette-Guérin (BCG) is the same one still in use today.

The first dose of this BCG was the culmination of 13 years of research and development.

BCG remains the only licensed vaccine against tuberculosis, and 2021 will celebrate its 100th anniversary.

Today, all eyes are paying attention to the development of the COVID-19 vaccine. However, while the number of people who died of COVID-19 last year is shocking, tuberculosis kills about the same number (about 1.5 to 2 million people) each year and has died for decades.

In fact, over the last 200 years, more than a billion people have died of tuberculosis, estimated to be far more common than any other infectious disease.

Why are so many people still dying from tuberculosis?

Tuberculosis is caused by Mycobacterium tuberculosis. It is transmitted when a person with active tuberculosis coughs an aerosol droplet and is inhaled by another person. There are about 10 million cases of active tuberculosis annually, and it is estimated that up to 2 billion people are known as “latent infections.” That is, they are not ill and do not infect the illness, but about 10% of these people will relapse.

In most TB endemic areas of the world, BCG is given to babies shortly after birth. Vaccination prevents childhood versions of tuberculosis and saves the lives of thousands of children each year.

However, the effectiveness of BCG declines over time. That is, it stops working. Protection against tuberculosis is often lost in adolescence or early adulthood.

Importantly, BCG does not prevent active pulmonary tuberculosis in adults, which is the most important cause of ongoing infection and death.

The World Health Organization aims to eradicate tuberculosis. To do this, we need to find a tuberculosis vaccine that works well in adults.

Need for a more effective tuberculosis vaccine

Over the last few decades, only about 15 new TB vaccine candidates have participated in clinical trials (against 63 COVID-19 in a year).

Worryingly, many of the most advanced tuberculosis vaccine candidates do not work better than BCG.

Due to the relatively small pipeline of tuberculosis vaccine candidates today, these setbacks and “failures” in trials mean that BCG may remain the gold standard for years to come.

Despite being 100 years old, little is known about how the BCG vaccine works. It is unclear why BCG usually provides only protection against tuberculosis in childhood or diminishes protection in adolescence.

Given these uncertainties, we are fortunate that the bureaucratic hurdles for vaccine development were significantly lower in the 1920s.

If BCG was developed today, it probably won’t be used. The current complex regulatory framework for vaccine development and licensing may disallow the use of vaccines for which little or little is known about the functioning of the vaccine.

The reasons why BCG was not replaced by a more effective tuberculosis vaccine are as follows:

• Reduction of tuberculosis in many Western countries in the 20th century

• Limited interest from pharmaceutical companies investing in tuberculosis vaccine development

• The fact that TB research and preclinical vaccine development are logistically difficult and require special biological containment facilities.

• The short-term and fiercely competitive environment for funding government and philanthropic research makes it difficult for scholars to engage in tuberculosis vaccine research as a career path.

The pace of COVID-19 vaccine development shows what is possible with political will, pharmaceutical interest and funding.

Tuberculosis is no longer widespread in Australia, but it is a problem in remote indigenous communities.

Papua New Guinea, the closest neighbor to Australia, has a high incidence of multidrug-resistant tuberculosis and low coverage of BCG. Tuberculosis has been introduced to Australia via the Torres Strait, with a high rate of cross-border diagnosis in northern Queensland and overestimation of indigenous children.

Resistance to current tuberculosis treatments is steadily increasing. Treatment of multidrug-resistant tuberculosis is very costly and can take up to 2 years and requires multiple antibiotics and close monitoring.

Now is the time to devote financial and political will to finding a more effective tuberculosis vaccine.

Last year (2020), we learned that pathogens can cause enormous damage to society and the economy. Investing in infectious disease research and vaccine development represents only a small part of the economic cost of a pandemic.

Tuberculosis is a global threat and a public health concern of the same magnitude as COVID-19. Instead of eradicating tuberculosis, it is essential to develop a new and effective tuberculosis vaccine to significantly reduce it.

BCG Anniversary is a celebration, but it should also help remind you that you need to do more to fight this deadly illness.

(Andreas Kupz is a Senior Research Fellow at James Cook University)

(Conversation / IPS)