Tuberculosis vaccine finds an improved route

A widely used vaccine against tuberculosis has now been shown to provide almost complete protection when injected intravenously. This is a striking improvement over vaccination through the typical intradermal route.

by Samuel M. Behar & Chris Sassetti

Tuberculosis is the deadliest human infection, killing 1.5 million people in 2018 alone ( It is widely accepted that an effective vaccine against the bacterium responsible, Mycobacterium tuberculosis, would be the most practical way to control the disease. However, the pathogen is often able to resist the immune responses elicited by vaccination. This has raised the question of whether it is possible for a conventional vaccine to confer sterilizing immunity against TB — a gold-standard immune status for vaccines, under which disease is prevented and the pathogen completely eliminated, often before it can even establish a productive infection. In a paper in Nature, Darrah et al.1 provide a resounding answer to this question by showing that near-complete protection from TB infection can be conferred using a century-old vaccine, simply by changing its route of administration.

The only currently licensed vaccine against TB is a live strain of the related pathogen Mycobacterium bovis, the virulence of which was attenuated in the laboratory between 1908 and 1921. The strain, known as bacille Calmette–Guérin (BCG), has been administered to more than one billion people ( since then (Fig. 1).

Image of Vaccine BCG ampullae.
Figure 1 | Ampoules of the BCG vaccine against tuberculosis. This vaccine has been used for almost a century, typically given as an injection just under the skin. Darrah et al.1 now provide evidence in monkeys that the vaccine’s efficacy can be greatly improved using intravenous injection.Credit: Alfred Eisenstaedt/AP/Shutterstock

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