Changing the administration of the BCG vaccine could improve efficacy

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Researchers have suggested that administering the tuberculosis vaccine, Bacille Calmette-Guerin (BCG), intravenously, as opposed to the standard intradermal route, could greatly increase the vaccine’s ability to protect from infection in rhesus macaque models.

Currently, the standard intradermal route of BCG vaccine administration protects infants from disseminated TB, but is less effective at preventing pulmonary TB – potentially owing to the vaccine not generating a strong enough T cell response in the lungs. In this study, the researchers suggested that intravenous or aerosol administration of BCG might overcome this hurdle and confer better protection.

To assess their hypothesis, the team administered the BCG vaccine via intradermal, intravenous or aerosol routes to groups of rhesus macaques and then assessed their immune responses via blood and lung fluid samples for a 24-week period post-vaccination.

After 6 months, the researchers exposed the vaccinated macaques to a virulent strain of Mycobacterium tuberculosis and tracked disease development over the following 3 months. Of the animal vaccinated with intravenous BCG, nine out of ten were observed to be highly protected, compared with significantly greater infection in unvaccinated, intradermal and aerosol groups.

Senior author JoAnne Flynn (University of Pittsburgh, PA, USA) commented: “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. Nine out of ten animals showed no inflammation in their lungs.”

The finding support investigation of intravenous BGC administration in clinical trials to determine if this might improve effectiveness in humans. Flynn concluded: “We’re a long way from realizing the translational potential of this work. But eventually we do hope to test in humans.”

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Sources: Darrah PA, Zeppa JJ, Maiello P et al. Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature 577, 95–102 (2020); www.upmc.com/media/news/010120-bcg-iv-vaccine

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