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Can a century-old TB vaccine steel the immune system against the new coronavirus?

Researchers in four countries will soon start a clinical trial of an unorthodox approach to the new coronavirus. They will test whether a century-old vaccine against tuberculosis (TB), a bacterial disease, can rev up the human immune system in a broad way, allowing it to better fight the virus that causes coronavirus disease 2019 and, perhaps, prevent infection with it altogether. The studies will be done in physicians and nurses, who are at higher risk of becoming infected with the respiratory disease than the general population, and in the elderly, who are at higher risk of serious illness if they become infected.

A team in the Netherlands will kick off the first of the trials this week. They will recruit 1000 health care workers in eight Dutch hospitals who will either receive the vaccine, called bacillus Calmette-Guérin (BCG), or a placebo.

BCG contains a live, weakened strain of Mycobacterium bovis, a cousin of M. tuberculosis, the microbe that causes TB. (The vaccine is named after French microbiologists Albert Calmette and Camille Guérin, who developed it in the early 20th century.) The vaccine is given to children in their first year of life in most countries of the world, and is safe and cheap—but far from perfect: It prevents about 60% of TB cases in children on average, with large differences between countries.

Vaccines generally raise immune responses specific to a targeted pathogen, such as antibodies that bind and neutralize one type of virus but not others. But BCG may also increase the ability of the immune system to fight off pathogens other than the TB bacterium, according to clinical and observational studies published over several decades by Danish researchers Peter Aaby and Christine Stabell Benn, who live and work in Guinea-Bissau. They concluded the vaccine prevents about 30% of infections with any known pathogen, including viruses, in the first year after it’s given. The studies published in this field have been criticized for their methodology, however; a 2014 review ordered by the World Health Organization concluded that BCG appeared to lower overall mortality in children, but rated confidence in the findings as “very low.” A 2016 review was a bit more positive about BCG’s potential benefits but said randomized trials were needed.

Since then, the clinical evidence has strengthened and several groups have made important steps investigating how BCG may generally boost the immune system. Mihai Netea, an infectious disease specialist at Radboud University Medical Center, discovered that the vaccine may defy textbook knowledge of how immunity works.