Could the TB vaccine in phase 3 trials in Malawi be a game-changer?

In December 2023, Amosi Kapoti suspected that something was terribly wrong with him. He had lost weight and developed a prolonged fever, and had been coughing for three weeks. He felt that each cough was heavier than the last.

The nights were the worst – often drenched in sweat, Kapoti said his bed felt like it had been soaked in water. “It was unbearable. I would struggle to catch my breath. It was like I was running, yet I was just sitting, and many times my feet were numb,” recalled Kapoti, the weight of the memories evident in his voice.

“If the vaccine trial turns out to be a success, a lot of lives will be saved and will reduce the number of TB cases that we usually register per year globally and locally.”

Patrick Goodson, researcher, Malawi Liverpool Wellcome Programme

Gripped by fear, he went to the hospital in Blantyre, Malawi’s second-largest city, for help. The doctor advised him to get a chest X-ray. The diagnosis was tuberculosis (TB), and Kapoti immediately began an intense six-month treatment regimen, consisting of eight tablets a day. “I thought my life was over,” said the 54-year-old. “It was just too much for me: taking such an amount of medicine every day for such a long time was not easy at all.”

Kapoti’s battle with TB came with a heavy price – his roof repairing and waterproofing business came to a standstill, leaving him unable to provide for his family. Much of his savings was spent on covering hospital bills.

Toll of TB

Globally, according to the World Health Organization (WHO), an estimated 10.8 million people fell ill with TB in 2023 and 1.25 million died. WHO says over 80% of cases and deaths are in low- and middle-income countries. In Malawi alone, around 25,000 people are estimated to develop TB each year. In 2021, an estimated 7,700 people died from the disease in the southern African country.

Despite the disease being one of the world’s deadliest infectious diseases and the leading cause of death among people living with HIV, the only currently available vaccine, BCG, has been in use since 1921 and is mainly given to babies and young children.

However, progress has been made to develop a new TB vaccine for adults. In March this year, South Africa became the first of seven countries to launch phase 3 of a TB trial vaccine known as M72/AS01E, funded by the Gates MRI, a nonprofit and subsidiary of the Bill & Melinda Gates Foundation, with support from Wellcome.

By September, Malawi had joined the initiative as the fifth country. Other participating countries in the study include Zambia, Mozambique, Kenya, Indonesia and Vietnam. The trial seeks to establish how effective it is in preventing the disease in adults.

The M72 vaccine has shown promise since its development in the early 2000s. A 2019 phase 2b trial revealed that it was safe, and demonstrated an effectiveness rate of almost 50% against progression to active pulmonary TB in adults, with the immunised showing an M72-specific immune response for three years.

The trial

In Malawi, the Malawi Liverpool Wellcome Programme is leading the phase 3 study at two sites: Gateway Malawi Liverpool Wellcome Clinic in Blantyre, and University of North Carolina clinic at Kamuzu Central Hospital in Lilongwe. Senior Research Clinical Officer on the trial in Malawi, Patrick Goodson, believes the vaccine, which aims to prevent latent TB from developing into TB disease, could be a significant addition to the world’s preventive healthcare arsenal.

“If the vaccine trial turns out to be a success, a lot of lives will be saved and will reduce the number of TB cases that we usually register per year globally and locally,” he said. “We are targeting people who are in the age range of 15–45 because this is the age group that is at risk of developing TB disease. The participants have to be healthy volunteers.” 

[Patrick Goodson, researcher, Malawi Liverpool Wellcome Programme]

The study aims to recruit 20,000 participants globally, while Malawi is set to enrol at least 692 participants, each receiving two doses of the vaccine.

“In October we began screening participants in the country for eligibility for the trial and now we have started recruiting the eligible participants. We have started well,” Goodson told VaccinesWork. “The trial is expected to take up to four years. Two years for recruiting participants, and two years for follow-up to see if they have developed TB after getting two doses.”

Goodson explained that a phase 3 trial is the last level of development before a vaccine can be evaluated for global market approval.

A burden beyond health

The need for a TB vaccine has never been more urgent. Nancy Kuntenjera, a nurse working in a TB ward at Nsanje District Hospital in southern Malawi, has seen the impact of the disease first-hand. She says the disease is not only a health burden for patients in Nsanje, but also an economic challenge, as many abandon treatments due to financial constraints.

“Since Nsanje borders Mozambique, some go there hoping to find a better life, but they stop their treatment because healthcare there is too expensive,” she explained. “Others simply cannot afford to stop working – they are breadwinners and feel they have no choice but prioritise their families’ needs over their own health.”

“A game-changer”

Dr Kuzani Mbendera, the Head of the TB Programme in the Ministry of Health, describes the TB vaccine trial as a potential “game-changer” in the fight against TB. “If all goes well, this vaccine will complement the efforts that we are carrying out as a ministry,” he told VaccinesWork.

One of these efforts is an intensified case-finding programme, which screens HIV-positive patients – a particularly at-risk cohort – for TB during their routine visits to antiretroviral therapy (ART) clinics. “With a million people living with HIV currently on treatment, that’s a significant number of individuals being regularly checked for TB,” said Mbendera.

“This is such a big step for our country,” he said. “If a vaccine was available, I’m sure I wouldn’t have gone through what I did. I wouldn’t wish my experience on anyone. This is good news.”

– Amosi Kapoti, TB survivor

The ministry is also employing TB preventive therapy, targeting those who are most likely to have an infection or are in conditions that are more likely for the disease to develop. “This is an area where we need to improve significantly,” Mbendera admitted. “We’ve done well with preventive therapy for people living with HIV, but not for those without the disease. The challenge lies in scepticism, as many people without active TB see little need for preventive treatment, and it’s still a relatively new programme.”

For Kapoti, after he completed his six months of TB treatment, he received a negative TB report this year. He says his “near death” experience has changed his perspective on life. “It has brought me closer to God. I am blessed to have had such big support from my family,”

Though he has not fully returned to work, Kapoti is optimistic that he will soon get back to what he loves to do – roof repairing. 

Upon hearing that Malawi is participating in a new TB vaccine trial, Kapoti smiled in amazement. “This is such a big step for our country,” he said. “If a vaccine was available, I’m sure I wouldn’t have gone through what I did. I wouldn’t wish my experience on anyone. This is good news.”