An urgently needed TB shot could democratise vaccines

Tuberculosis surrendered the title of the world’s deadliest infectious disease after COVID-19 struck, but it reclaimed that terrible distinction last year. As with COVID, a new vaccine could go a long way to sharply curtailing the disease, which killed about 1.4 million people a year before the pandemic and increased its deadly toll a bit after COVID took hold.

Scientists in South Africa and the US, along with the South African company Afrigen Biologics & Vaccines, have come up with a promising new strategy for a tuberculosis vaccine, and while there’s a long road ahead to bring the shots to market, a successful effort could yield an important new tool against the deadly pathogen.

Equally important, the project could lay the foundation for a vaccine discovery and commercialisation network being built in South Africa and in other low- and middle-income countries. During COVID, the world witnessed the devastating consequences of poor countries having to wait on rich ones to share vaccines. A successful homegrown TB vaccine could be a first step in reducing that reliance on wealthier nations — for current infectious diseases and whatever threats arrive next.

The only TB vaccine available today is a 100-year-old product that can be used solely in babies and small children, and even in those groups it doesn’t always work. To have any chance of meeting the World Health Organization’s goal of reducing TB cases by 80% and deaths by 90% by 2030, “we need a new vaccine,” said Lucica Ditiu, the executive director of the Stop TB Partnership.

Getting to one has been painfully slow. The bacteria responsible for TB has spent several millennia evolving to hide out from the human immune system. Moreover, its genome encodes for thousands of proteins; picking the right ones for a vaccine that would give immune cells the best target practice for future infection has been an arduous task.

So while more than a dozen vaccines are in development, the WHO noted in a recent report that there is “little antigenic and immunological diversity” among them. In plain language, that means they are all designed to show the immune system the same few proteins. The best of those vaccines, a shot developed by GSK Plc, has so far proved only modestly effective.

Even a modestly effective one could still save many lives, but given the burden of TB, we need to keep pushing for something better. The team in South Africa might just have a good idea for that.

Its vaccine discovery was rooted in a simple question: Why do some people infected with TB become very ill while others don’t? The South African researchers collected samples over two years from teenagers who were infected with TB, with the aim of comparing the immune responses between those who went on to have active disease with those whose immune systems were able to control the infection.

But they didn’t have a good way to pull useful information out of the patient samples, which were relegated to a deep freezer for years. That is, until they teamed up with researchers at Stanford University who had devised a technique for analysing which T-cell response was most common in the people whose infections were controlled as well as the TB proteins those immune cells were zeroing in on. The group eventually identified four key proteins that seemed connected to staving off TB.

That technological advance coincided with two other developments: the incredible progress in the field of mRNA vaccines during COVID and an investment from the WHO in an mRNA vaccines hub in South Africa. Although the hub was initially focused on COVID vaccines, it has turned its attention to TB, which before COVID was the leading cause of death in the country.

Afrigen and its academic partners are testing several different vaccine designs in mice, comparing the immune response from each of the individual antigens identified by the researchers with the response elicited by various combinations of them. The hope is that one design emerges as a clear winner and that the team can move on to tests in monkeys, which are a much closer proxy to humans than mice.

Whatever mRNA vaccine they land upon can’t simply work — it also needs to be affordable and distributed easily. That will require substantially lowering the overall cost of goods for making the shots and coming up with ways to keep them stable at lower temperatures.

If all those hurdles are cleared, the next big challenge will be funding human studies. Proving a TB vaccine works requires huge trials. A simulation conducted by the Bill and Melinda Gates Medical Research Institute, which licensed GSK’s TB vaccine in 2020, suggested a Phase 3 trial would need to enroll at least 13,000 people living in a setting with a high prevalence of TB cases to show its vaccine is effective.

Petro Terblanche, the chief executive officer of Afrigen, feels “absolute surety” that if they reach that point, funders will come forward. Overcoming the immense burden of TB is a high priority for public health agencies, and she believes the localised manufacturing of the vaccine will be added motivation for philanthropies and other groups to support the project. Given the historic underfunding of this scourge, I hope Terblanche turns out to be right.

And then there’s the issue of intellectual property. Afrigen’s initial efforts for a COVID vaccine relied heavily on designs described in Moderna’s patents. And while the team is trying to create some of its own intellectual property, Terblanche acknowledges that eventually the group will have to engage with Moderna and others to obtain the licenses needed to operate. “That hill is still to be climbed,” she says.

This is just the start of a long journey for Afrigen and its partners. But if they succeed, their victory will not only be one for TB but also one for improving health equality for other infectious diseases.

Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). It is named after its inventors Albert Calmette and Camille Guérin. In countries where tuberculosis or leprosy is common, one dose is recommended in healthy babies as soon after birth as possible. In areas where tuberculosis is not common, only children at high risk are typically immunised, while suspected cases of tuberculosis are individually tested for and treated. Adults who do not have tuberculosis and have not been previously immunised, but are frequently exposed, may be immunised, as well. BCG also has some effectiveness against Buruli ulcer infection and other nontuberculous mycobacterial infections. Additionally, it is sometimes used as part of the treatment of bladder cancer.



Agencies