New TB vaccine: mid-phase trials confirm safety, long-term prevention

By Dr. Liji Thomas, MDOct 30 2019

A new study published on October 29, 2019, in the New England Journal of Medicine, reports a new vaccine which could change the face of tuberculosis prevention. The disease kills 1.5 million people worldwide each year.

The results were presented at the 50th Union World Conference on Lung Health in Hyderabad, India. The summit was convened by the International Union against Tuberculosis and Lung Disease. The prime benefit of the new vaccine is its ability to bring about a more robust and durable immune response that can potentially keep the immunized individual safe from tuberculosis lifelong.

A multinational team of researchers formulated the new vaccine using bacterial proteins and adjuvants which trigger a strong immune response. Calling it a “game-changer”, tuberculosis expert David Lewinsohn pointed out that the vaccine prevented the development of tuberculous disease in people who were already infected with the bacteria.

More trials on larger and more diverse groups will be necessary, in all probability, before licensing requirements are fulfilled, according to the researchers. They are confident that the results of such trials will confirm earlier results, leading to its approval. If so, says Lewinsohn, “This vaccine has the potential to revolutionize TB treatment.”

About tuberculosis

There are about 10 million people in the world with tuberculosis, according to 2018 figures released by the World Health Organization. Caused by the bacterium Mycobacterium tuberculosis, the disease leads to the formation of chronic inflammatory granulomas which erodes normal lung tissue and causes severe destruction. The condition spreads quickly from person to person, through tiny droplets in cough or sneeze aerosols. It can be prevented only by the Bacille Calmette-Guerin (BCG) vaccine or by the use of powerful anti-tuberculosis drugs following known potential exposure. Most adults are infected with M. tuberculosis, but the resulting conversion to active disease occurs in a very few, for reasons which are still unknown. This has led scientists to postulate that the bacterium induces natural immunity in the vast majority of infected people.

Mycobacterium tuberculosis is a pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of most cases of tuberculosis - Illustration Credit: Tatiana Shepeleva / Shutterstock

Tuberculosis commonly causes lung disease but is also well known to affect the abdomen, lymph glands, bones and the central nervous system (brain and spinal cord). Lung tuberculosis is suspected when the individual has a persistent cough for over 3 weeks, weight loss for no reason, fever, and night sweats.

When the infection is present but there is no active disease, it is called latent tuberculosis – a condition seen in about 25% of the world population. The individual with latent tuberculosis infection has inactive bacteria in the body, but is neither sick nor contagious. However, the lifetime risk of active tuberculosis is 5% to 10%.

Tuberculosis is treated using anti-TB drugs, which need to be taken in combination for periods of 3-6 months. However, a major threat that has arisen in recent decades is multi-drug tuberculosis (MDR-TB). In this condition the bacteria do not respond to two or more first-line tuberculosis drugs, making it more difficult and costly to treat.

India – world hub for tuberculosis

2 of every 3 people with tuberculosis hail from just 8 countries – the highest contributor, by far, being India with well over a quarter (27%) of the world’s total cases. Each year, India sees almost 3 million new cases, with MDR-TB accounting for 100,000 of them. Tuberculosis management costs the exchequer about $24 billion a year, despite which the disease claims the lives of 400,000 Indians each year.

It is therefore no bombastic statement when Jamhoih Tonsing, head of the International Union against Tuberculosis and Lung Disease, says, “We cannot eliminate TB globally unless we end it in India.”

In its wake come China with almost 10%, Indonesia with 8%, the Philippines and Pakistan with 6%, Nigeria, Bangladesh and South Africa with 3-4% each.

WHO targets for world tuberculosis include a 90% reduction in new cases, and 95% reduction in tuberculosis deaths, between 2015 and 2035. These targets are difficult to achieve unless a powerful vaccine is available, given the insidious onset of the disease and its high spread among contacts of the sick person.

M72/AS01E – solid promise

The BCG vaccine is recommended by the WHO and has been in use since 1921 in most parts of the world to immunize children against tuberculosis, but its efficacy is limited in protecting high-risk adults against infection, and moderately effective in children and infants. In the face of growing drug resistance and research findings which suggest that adolescents and adults should be targeted by immunization to stop the advance of tuberculosis, vaccine development has been a high priority.

The new GlaxoSmithKline (GSK) vaccine, called M72/AS01E, has been under development for over 20 years. The current phase 2 clinical trial showed long-term protection (for 3 years after vaccination) and solid evidence of safety and at least 50% efficacy in protection against active disease.

The trials were conducted on over 3500 HIV-negative adults between the ages of 18 and 50 years, in many parts of South Africa, Kenya, and Zambia which experience a high endemicity of the disease. They received 2 doses of the vaccine or placebo at an interval of 30 days, and were followed up for 3 years. The effectiveness did not appear to be compromised by an older age.

Almost 50% of participating adults were protected against the development of active tuberculosis from the already existing bacteria in their bodies. This validated earlier 2018 trials findings and signposted the progress of the vaccine towards meeting the demand for an adult/adolescent vaccine that meets the recommendations of the WHO’s ideal vaccine. GSK’s chief medical officer of vaccines, Thomas Breuer, says, "These results demonstrate that for the first time in almost a century, the global community potentially has a new tool to help provide protection against TB.”

Much more work remains, of course, with the earliest date for vaccine release being 2028. Vaccine studies on tuberculosis often involve much larger trials than are necessary for acute viral illnesss like measles. This is because vaccine efficacy must be proved in animals, such as mice, guinea pigs and non-human primates. Again, animal models are not accurate in reflecting the progress of the disease or in the kind of response the vaccine should have in a human model. By way of example, say the researchers, tuberculosis is an indolent disease in mice. In these models, therefore, rather than going by clinical indicators of success, a ten-fold reduction in bacterial count in lung tissue might be interpreted as vaccine success. However, in human beings, this is not a desirable outcome: having even 10% of the bacteria is still equivalent to having the disease. Hence the actual clinical efficacy in terms of preventing active disease is the outcome that needs to be modeled in a variety of settings, to establish robust evidence of vaccine success.