Can well-known TB vaccine increase resistance to coronavirus?

Clinical trials start in four countries

Researchers in four countries will soon start a clinical trial of an unorthodox approach to the new coronavirus, Jop de Vrieze, a science journalist in Amsterdam, wrote to Science Magazine this week. 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. They will recruit 1000 health care workers in eight Dutch hospitals who will either receive the vaccine, called bacillus Calmette-Guerin (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 Guerin, 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

BCG vaccination protects against experimental infection with a weakened form of the yellow fever virus, which is used as a vaccine. Together with Evangelos Giamarellos from the University of Athens, Netea has set up a study in Greece to see whether BCG can increase resistance to infections overall in elderly people. He is planning to start a similar study in the Netherlands soon. The trial was designed before the new coronavirus emerged, but the pandemic may reveal BCG’s broad effects more clearly, Netea says.

A research group at the University of Melbourne is setting up a BCG study among health care workers. Another research group at the University of Exeter will do a similar study in the elderly. And a team at the Max Planck Institute for Infection Biology last week announced that,inspired by Netea’s work, it will embark on a similar trial in elderly people and health workers with VPM1002, a genetically modified version of BCG that has not yet been approved for use against TB.

Eleanor Fish, an immunologist at the University of Toronto, says the vaccine probably won’t eliminate infections with the new coronavirus completely, but is likely to dampen its impact on individuals.

Annie Sparrow, an assistant professor of population health science and policy at Icahn School of Medicine at Mount Sinai in New York told Foreign Policy that several studies in other contexts show that BCG primes the immune system to respond better to infections of various sorts, not just TB. Two studies in adults (one in patients aged 60 to 75) showed that BCG reduces respiratory infections by 70 to 80%. Two more reported a 15 to 40% lower risk of respiratory infections in vaccinated children. Another showed that, when given to infants in countries with severe health challenges and combined with a revived immunization scheme, BCG cut deaths from all causes by just under a third. However, some studies suggest that this protective effect lasts only until an inactivated vaccine (such as an influenza vaccine) is later given.

Even if BCG vaccines were given only to health workers, we might substantially reduce the risks they face and lessen the risk of our hospitals and health systems collapsing, Sparrow said. If effective, it could also be rapidly given to other particularly vulnerable people such as the elderly. It could be especially useful in countries that have weak health care systems and would quickly be overwhelmed by a large outbreak. And the vaccine is cheap, safe, and, most important, immediately available for testing.

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