The South African Medical Research Council (SAMRC) Pneumococcal Diseases Research Unit met its transformative match in Professor Shabir Madhi. Under his leadership, the unit moved from a primary focus on epidemiology and vaccines against Streptococcus pneumoniae, to a rebranded SAMRC/Wits (University of the Witwatersrand) Vaccines and Infectious Diseases Analytics Research Unit (Wits-VIDA) that is  internationally recognised for research on vaccine-preventable diseases. 

The unit also expanded its research to other respiratory and enteric pathogens and evolved to include basic science research, clinical immunology of vaccine-preventable diseases, ongoing epidemiology studies across a range of diseases, and the clinical development of vaccines targeted at children, pregnant women, and, most recently, COVID-19.

“My research into preventable diseases and vaccines started in 1997 when I got involved in a programme that helps evaluate the pneumococcal conjugate vaccine,” says Madhi. “At the time, this was the largest clinical trial undertaken outside of North America and was targeted at children. The goal was to prevent the leading cause of under-five child mortality from any single organism.”

Madhi’s team enrolled about 40 000 children over a two-and-a-half-year period and provided the first evidence of the effectiveness of the vaccine in preventing new pneumococcal disease. After that, he went on to get involved in a number of vaccine studies that have contributed to World Health Organization (WHO) recommendations on the use of vaccines, particularly around the use and deployment in low- and middle-income countries.

“Another stand-out moment was our work on the rotavirus vaccine that targets the leading cause of deaths from diarrheal disease in children under the age of five,” says Madhi. “Again, it was the first study undertaken in a low-middle income country that demonstrated the value of the vaccine, reducing diarrheal disease.”

Before COVID-19 struck, Professor Madhi was focused on maternal vaccinations aimed at protecting both the mother and the foetus, as well as the infants in the first three to six months of life.  

“Some of the first studies we did, once again leading on the global stage with research done in South Africa, included looking at vaccines in both pregnant women living with HIV and protecting against influenza,” he explains. “We demonstrated that you’re able to protect both the mothers and the babies from becoming infected and developing influenza by vaccinating the mothers.”

The professor’s unit was also involved in the first study on respiratory syncytial virus (*RSV) which is the most common cause of hospitalisation of children in high-income and low-middle income countries for lower respiratory illness. It is responsible for around 35-40% of children ending up in hospital, and usually within the first six months of their life. The team assumed a leading role in the first global study on the RSV vaccine in pregnant women and showed the potential of vaccination in protecting babies in the first six months of life. These three studies underscore some of the impressive strides that Madhi has made in his career, and yet they are only the tip of the proverbial iceberg.

“We are also recognised to be global leaders in another maternal immunisation study against Group B streptococcus (GBS), which is the leading bacterial cause of sepsis in the first three months of a child’s life, especially in high-income countries, as well as in low-income countries,” he says. “In fact, in high-income countries, GBS has become the leading cause of meningitis in children and most of that occurs in the first three months of life. It is also a leading cause of neonatal sepsis in lower-income countries, and especially in Africa. We’ve been working on the research to develop vaccines against GBS and we’ve recently completed the first global studies in pregnant women with and without HIV.”

Then COVID-19 entered the picture and it’s very easy to see why Professor Madhi and Wits-VIDA turned their focus towards this new virus. It made sense to make this shift, particularly considering that the research he’d been engaged with had largely been focused on respiratory pathogens.

 “Using our experience from the past 27 years, we transitioned to undertaking the first COVID-19 studies on the African continent including the AstraZeneca vaccine, which is currently the most widely-used vaccine against COVID-19,” explains Madhi. “We did the studies around this vaccine and the Novavax vaccine and it gave us the insights we needed to recalibrate our expectations around COVID-19 vaccines. Over the past 18 months, we’ve uncovered that the virus has developed antibody evasiveness and none of the vaccines provide sustainable protection against mild to moderate COVID-19 as a result.”

The research also found that the vaccine protectiveness diminishes over time due to mutations and the waning of the antibody. So, the studies were critical in laying out the COVID-19 scenario and making tangible plans for the future of vaccines globally.

Professor Madhi is awarded the Lifetime Award  because of his level of expertise and impactful innovation in his professional repertoire, but this just scratches the surface of the work he’s done and his commitment to this unit and its research. Around 95% of Wits-VIDA research funding, which totals around R1.5-billion between 2014 and 2022, is from grants and other self-initiated research activities — all led by Madhi. The grant funding allows for the employment of 500 staff that include research assistants, nurses, doctors, scientists, data analysts and statisticians. The research scope is strengthened even further by using the platform as a training ground for postgraduate students, with a focus on PhD and clinician scientists. 

The research unit is located in dedicated facilities at the Chris Hani Baragwanath Academic Hospital and includes clinical space for vaccine studies, with Wits-VIDA having established itself as a premier research unit in the field of phase I-IV vaccine trials. Over the past 27 years, the unit has also established a fully-fledged immunology, microbiology and molecular assays laboratory. Although Wits-VIDA has an extensive network of collaborators globally, these collaborations are underpinned with Wits-VIDA being lead partners on most of the studies and generally enabling the growth of research in South Africa. 

All of the research highlighted above was led by Professor Madhi, and undertaken exclusively in South Africa. The clinical trials included grant-funded pivotal studies and Madhi took on a strategic role with industry partners to drive other vaccine studies, as he’s recognised as an expert in the field. 

Professor Madhi has taken his passion and commitment to changing vaccine outcomes and saving lives to the next level with his work. The NSTF-South32 Lifetime Award is a well-earned crown on his extensive work, the transformative impact he has had on South Africa’s public health and his ongoing dedication. 
— Tamsin Oxford

Read the special Mail & Guardian supplement about all the NSTF-South32 Award winners.