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Wits Fulbright Scholar Pioneers Development of Gene-Edited Tuberculosis Vaccine

- FHS Communications

Emerging researcher Moagi Shaku worked closely with Professor Bavesh Kana, head of the Wits School of Pathology, to conceptualise a breakthrough and innovative tuberculosis vaccine that can be used across the life course.

Emerging researcher Moagi Shaku

While Shaku is currently a post-doctoral fellow at Johns Hopkins University School of Medicine in the USA, his affiliation with the Centre of Excellence for Biomedical TB Research based at Wits University, allows him to work on innovative solutions to combat tuberculosis and its broad-ranging social and economic effects.

Tuberculosis is one of the oldest and most infectious bacterial diseases. In 2022, 10.6 million people fell ill with it. Of these infections, 23% occurred in Africa.

“TB vaccines are hard to develop because the bacterium that causes the disease is complex and learns to outsmart the immune system. We have only had the BCG (Bacillus Calmette-Guerin) vaccine to combat the disease, administered in early childhood. But that’s about to hopefully change. We have made a significant breakthrough in using CRISPR (gene editing technology) to make a vaccine effective in adults too,” said Shaku.

Shaku studies the physiology of Mycobacterium tuberculosis to identify and validate novel TB drug targets and apply this knowledge to develop novel TB vaccines. Specifically, he's developed a recombinant BCG vaccine with properties aimed at enhancing trained innate immune responses against infection with Mycobacterium tuberculosis. 

Professor Bavesh Kana credits Shaku with considering the use of CRISPR technology. “We observed that the cell wall features a small chemical decoration on its surface, which allows bacteria to conceal an important marker known as the NOD-1 ligand from the immune system. Both the tuberculosis and the live bacteria used in the BCG vaccine can hide the NOD-1 ligand from the immune system, making it harder for the body to detect them. Moagi thought of modifying the BCG bacterium, so it can’t hide this NOD-1 ligand,” said Kana.

Shaku added that to investigate this possibility, the team turned to CRISPR, to allow scientists to modify DNA. “So far, mice vaccinated with this modified BCG vaccine were more adept at limiting TB growth in their lungs than those mice that received the original vaccine.”

He says that the scientific expertise around TB in South Africa is commendable and world class.

“Our findings present a promising new vaccine candidate for tuberculosis. With innovative vaccines in development, we can better address this serious disease. This research highlights gene editing as a powerful tool in vaccine development, potentially improving vaccines for other diseases as well,” concluded Kana.

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