M72: Three things you need to know about a TB jab that might work

The only anti-tuberculosis shot we have is the century-old BCG vaccine given to infants, whose protection only lasts for 10 to 20 years. (Photo by Paul Kane/Getty Images)

Phumeza Tisile, now 33, lost her hearing because of the drugs she had to take to cure her of tuberculosis (TB). But had an adult vaccine against TB been available, chances are she might not have fallen ill in the first place.

A cash injection of just over R10 billion could bring us one step closer.

In late June, the Bill & Melinda Gates Foundation and the Wellcome Trust announced that they will, together, contribute this money for the next phase of a clinical trial to test how well a new vaccine, called M72/AS01E, works to stop people from getting sick with TB. 

A vaccine is something that looks to the body like a disease-causing germ, but without making you sick. It triggers the immune system into making antibodies that can fight an infection when the real germ is encountered. 

Although there are more than a dozen other potential TB vaccines being developed at the moment — all in different stages of testing and for different purposes — M72 is the first one to show real promise for helping to end TB. 

We break down how it works and why it’s worth getting excited about. 

1. Why having a shot at a new vaccine is big news

Results from 39 people in a previous round of tests to see if the vaccine is safe and works the way researchers planned it to work, showed that the candidate vaccine could protect at least half of people who are infected from falling ill with TB, also called active disease. 

People who are infected with TB but who don’t show signs of the illness are said to have a latent infection rather than active disease.

It’s the first of the new jabs being experimented with that could potentially reach this level of effectiveness across large groups of people.

A phase 3 clinical trial, as is on the cards for M72 now, means a medicine is tested in thousands of people to see how well it works to protect someone against developing active TB and whether it causes any serious side effects that could make it unsafe to use. 

Getting a new jab on the market is expensive, though — one of the reasons the World Health Organisation (WHO) says we’re still having to rely on the 1921-developed Bacille Calmette-Guérin (BCG) vaccine as the only shot to protect people from getting sick with TB. 

Moreover, the BCG jab can only be given to children who don’t have the TB germ yet. In South Africa, all babies get this shot when they’re born. Although the vaccine protects young children against getting sick with TB, its shielding effect wanes after about 15 years, meaning people are vulnerable to getting ill from the time they’re teenagers. 

This next stage of testing, which could run until 2029, will include both HIV-positive and negative people between 18 and 50 years old, as well as people with or without TB infection across South Africa, Kenya and Zambia. 

The previous round of testing, also in these three countries, included only HIV-negative people with latent infection. Having had a childhood BCG jab did not affect whether someone could take part in that round of testing.

2. Less illness, fewer deaths and more savings 

Worldwide, about 10.6 million people got infected with TB in 2021, with 10% of them dying. Poorer countries such as in Africa and Southeast Asia bear the biggest brunt, especially those where many people have HIV as the virus weakens the body’s immune system and so makes it difficult to keep TB germs from getting out of hand. 

In South Africa, about 300 000 new TB infections and 56 000 deaths were counted in 2021. The country, along with seven others, accounted for two-thirds of TB cases in the world. Compare  this with 210 000 new HIV infections here in 2021 and 51 000 Aids-related deaths. 

The WHO estimates that in the next 25 years, a vaccine like M72, which can be given to teens  and adults, can prevent up to 76 million cases of TB disease and at least 4.6 million deaths. As many as 42 million fewer courses of antibiotics would be necessary for treating TB and across the world households could save around R745 billion in dealing with the disease and its fallout. 

TB is preventable and curable — but it has to be picked up and treated early to stop infections from spreading or the bug can become resistant to drugs used to thwart it. About a quarter of the world’s population is infected with TB worldwide, but only a small proportion will become sick.

Studies have shown that treating drug-resistant TB (that is, a form of the disease for which the normal antibiotics don’t work) can cost 25 — and in some cases 100 — times more than when the standard type of drugs can be used. Moreover, even when people are cured, many battle with the fallout from the disease for long after, in some cases even for the rest of their lives.  

3. The new kid on the block

The M72 vaccine is made up of two proteins of the germ that causes TB. The proteins are plugged into a carrier cell and linked with other ingredients, called adjuvants, which make the shot stronger. The jab prompts the immune system into making antibodies that will fight and kill the bacteria.

A vaccine made of the complete (but inactive) disease-causing bug, such as the BCG jab, usually leads to a strong immune reaction. But in newer shots, generally only parts of the bug are used to prod the body to make antibodies because they’re thought to be safer, especially for people who have weak immune systems. 

But such vaccines might not trigger as strong an immune reaction, which means they might not be useful to give when the body will be exposed to a bug the first time. Rather, they’re good for boosters (a shot after your first one, to bolster its protection), such as with the BCG vaccine.

However, because the protection from BCG lasts only for about 10 to 20 years, the way M72 works could make it well suited as a booster shot and protect adults and teenagers against TB disease. 

Other candidates that are also in the running are MTBVAC, which uses a live but inactive form of the TB germ. Meant to be given to newborns of either HIV-positive or negative moms, it’s shown promising results in early clinical trials. MTBVAC is currently in phase 3 testing, like M72. 

Another option is VPM1002, currently also in a combined second and third round of clinical tests in India, where researchers are looking to see how well it works to keep people who have been cured from TB from getting sick again. This vaccine is meant for newborn immunisation as well as for adults who have previously had the shot.   

The Bill & Melinda Gates Foundation (BMGF) is mentioned in this article. Bhekisisa receives funding from the BMGF, but is editorially independent. 

This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.