100 years of TB vaccine and yet the killer is still among us
As TB continues to be a top killer across the world, we urgently need a new vaccine
In 1921, the first effective tuberculosis (TB) vaccine was used on human subjects to help protect against this lethal disease. Yet, 100 years later in 2021, more than 1.6 million people died from TB across the world, according to the World Health Organization (WHO), making it the top killer infection once again. There is now an urgent need for new vaccine options to help stop this historical killer.
TB is caused by the Mycobacterium tuberculosis bacterium and is spread by inhaling respiratory droplets released by infected people when they cough or sneeze. These droplets can stay suspended for long periods of time, meaning contamination remains a risk even after the infected person has left the room. The disease mostly affects the lungs, but in some cases it can attack other areas such as the glands, bones, kidneys, and nervous system. Although TB is often lethal if left untreated, it can be cured with antibiotics and antimicrobial drugs.
Until the early twentieth century, TB was one the most common causes of death, especially among poorer communities in cramped urban locations. Then, in 1921, Albert Calmette and Jean Marie Camille Guérin developed their TB vaccine – the Bacillus Calmette-Guérin vaccine (BCG) – and used it on human patients (an infant who had been in close contact with a TB patient). This was the first effective vaccine to protect the lungs from TB and became the standard vaccine from then on.
The slow development of new alternative vaccines has not been caused by a lack of interest. There are currently more than 10 TB vaccines in development, with some of them nearing the end of the clinical trial phase. The issue is that, according to a statement by Frank Cobelens, Professor of Global Health at the University of Amsterdam and the Amsterdam Institute of Global Health and Development (AIGHD), “TB vaccine research and development is hampered by our limited knowledge of protective immune responses, poor prediction of efficacy in humans by animal models and lack of correlates of protection (the immune response required to give protection)”.
This basically leads to a higher-risk pipeline that includes large, expensive trials over long durations. “Essentially, we don’t know if vaccines will work until they are at the end of the clinical trials process”, Cobelens added, “meaning high-risk, high cost.”
Despite these issues, there are signs of hope on the horizon. One potential approach involves an alternative route of delivery for BCG-vectored vaccines. This includes individual antigens being delivered by viral vectors or with adjuvant, an ingredient used to help create a stronger immune response from a vaccine, and a live genetically modified M. tuberculosis itself.
Examples of contending vaccines include M72/ASO1, an adjuvant vaccine, that has so far shown effective protection among infected adults and has been used in a trial of around 3,500 participants in Kenya, South Africa and Zambia. The vaccine has demonstrated 50 percent protection against TB infection after a three-year follow-up and was also successfully tested on 400 people living with HIV.
Another frontrunning contender is a Russian vaccine, GamTBVac, which has passed into phase 3 clinical trials with 7,000 participants expected to report their results in about 2025. There is also the VPM1002, a live recombinant BCG vaccine that involves the use of a live weakened bacterial strain, which is set to report on the results of trials in babies and the prevention of recurrence in adults in two years.
The WHO’s 2022 Global Tuberculosis Report can be found here.
Source: IFLScience
