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Intravenous BCG: 'The effects are amazing'

Stethoscope and a world map

24 March 2020

Today is World Tuberculosis Day. Worldwide, more people die from Tuberculosis (TB) than any other infectious disease, even though the vast majority of people are vaccinated. Researchers have found that changing the way the vaccine is administered might the key to improving its efficacy.

Muriel Cozier

Administering the TB vaccine intravenously in monkeys has been found to provide better protection than the usual injection done under the skin. Researchers at the University of Pittsburgh School of Medicine and the National Institute of Allergy and Infectious Diseases (NIAID) tested several routes and doses of the only commercially available human TB vaccine, BCG (Bacille Calmette-Guérin). The vaccine is made of a live, weakened form of TB bacteria found in cattle. The vaccine has been around for close to a century and is among the most widely used vaccines in the world, but its efficacy varies widely.

The idea to deliver the vaccine intravenously came from work done on delivering the malaria vaccine in this manner. It had been shown that administering the malaria vaccine intravenously made it more effective in both humans and animals.

To assess the effectiveness of different methods of administering the vaccine, researchers separated a colony of monkeys into six groups, these being : unvaccinated, standard human injection, stronger dose but same injection route, mist, injection plus mist and finally a stronger dose of BCG delivered as a single shot directly to the vein. Six months later the animals were exposed to TB and monitored for signs of infection.

It was found that the monkeys receiving a dose intravenously had almost full protection against TB, with virtually no TB bacteria found in their lungs. The other five groups all showed signs of infection. The researchers noted that one month after vaccination; BCG and activated T- cells were present in the lungs of the monkeys that received intravenous injections. In the other groups BCG was undetectable in the lung tissue and T-cell responses were ‘relatively meagre.’ T-cells are important to the body’s immune response.

JoAnne Flynn, Distinguished Professor of microbiology and molecular genetics and a member of Pitt’s Centre for Vaccine Research said ‘The effects are amazing. When we compared the lungs of animals given the vaccine intravenously versus the standard route, we saw a 100 000-fold reduction in bacterial burden.’

Future studies will look at whether lower doses of intravenous BCG could offer the same level of protection without the side effects, which mainly consists of temporary inflammation in the lungs. The research has been published the journal Nature.

While the results have proved to be source of excitement, Flynn sounded a note of caution. ‘We’re a long from realising the translational potential of this work. But eventually we do hope to test on humans.’

Nature: DOI:10.1038/s41586-019-1817-8

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