Delivering tuberculosis vaccine directly to veins may boost protection

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Is there a better way to deliver the TB vaccine?

VOISIN / PHANIE / SCIENCE PHOTO LIBRARY

Delivering the only vaccine against tuberculosis via veins rather than into the skin can dramatically increase its potency and could be a “game changer” in eradicating the disease.

Tuberculosis (TB) is the world’s leading cause of death from infection, killing 1.5 million people each year. But the BCG vaccine, which has been around for 80 years and is given at birth or early in life, isn’t very effective against TB infections via the lung as people age.

Robert Seder at the National Institute of Allergy and Infectious Diseases in Maryland and his colleagues found this could be because of the way the vaccine is delivered. The standard approach is to inject it into the skin. But it turns out to be far more effective when it is delivered directly to a vein.

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Nine out of 10 monkeys that had the vaccine intravenously were protected from the disease when exposed to it six months later. Just two out of 10 monkeys that received the vaccine into the skin were protected. Monkeys given the vaccine via veins also showed much higher levels of T-cells in the lungs, a key part of the immune system’s protection against TB.

Straight to the lungs

The reason for the difference seems to be that giving the BCG vaccine in the skin generates T-cells locally there, and only some of these circulate to the lungs where they can combat a TB infection. The intravenous route sees the vaccine go into lymph nodes around the body, and also into the spleen and the lungs, where it generates T-cells at the site of infection.

Tests in humans could be around 18 months off, says Seder. There are still issues to iron out – for instance, it might be hard to organise a mass inoculation programme that delivers a vaccine directly to the vein. There are safety considerations too. “It’s potentially a game changer if we show we can administer it safely,” says Seder.

Punam Mangtani at the London School of Hygiene & Tropical Medicine says the work is a “very interesting proof of principle” and could mark a “step change” in research. However, she cautions the response could be different in people and says safety will be key.

Helen McShane at the University of Oxford says the results, which builds on one study in the 1970s and another in 2016, are exciting. But she is cautious about the prospects of routine use in people.

For one thing, the monkey tests don’t show what protection an intravenous BGC vaccine would give at adolescence, on top of the usual BCG given at at birth, because the monkeys weren’t given it at birth. She also notes other possible challenges, not least that where TB is endemic, there are high rates of HIV, meaning people may be fearful of intravenous injection.

Journal reference: Nature, DOI: 10.1038/s41586-019-1817-8

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