A Century-Old Vaccine Fails to Protect Against Covid

An old tuberculosis vaccine known to bolster the immune system did not prevent Covid infections among health care workers, scientists reported on Thursday.

But the trial was shorter and smaller than originally designed, and the investigators said that the results did not rule out other potential benefits associated with the vaccine, known as B.C.G. for bacille Calmette-Guerin.

The study, published in The New England Journal of Medicine, was the largest clinical trial of the vaccine’s potential to protect against Covid infections. B.C.G. was developed in the early 1900s to combat TB, but has since also been shown to confer protection against other illnesses, including respiratory diseases.

The trial of health care workers began in March 2020, during the early days of the pandemic, when no effective treatments for Covid were available and a new vaccine against the highly infectious disease seemed to be a remote fantasy. The hope was that the old vaccine might be repurposed to save lives.

Six months after vaccination with B.C.G., however, there were no significant differences between the two groups of health care workers: While 14.7 percent of those inoculated with B.C.G. developed symptomatic Covid infections, 12.3 percent of those who received saline placebo shots got sick.

Five participants in each group were hospitalized, and one participant who got the placebo died. The differences were not statistically significant.

The remarkably rapid development of mRNA vaccines made it impossible to complete the B.C.G. trial as designed because health care workers were first in line to get the newly available mRNA shots.

The goal of the B.C.G. trial had been to follow 10,000 participants from five countries — Australia, the Netherlands, Spain, Britain and Brazil — for 12 months, but the new paper reports on only 4,000 adults who were followed for six months.

The mRNA vaccines were “an absolute miracle of modern science,” said Dr. Nigel Curtis, the trial’s chief investigator, who is a professor of pediatric infectious diseases at the University of Melbourne in Australia. “But from the trial’s point of view, it was fairly disastrous.”

A still larger trial would have been required to see whether the vaccine protected against not just infections but also hospitalizations and deaths from Covid.

The vaccine is still widely used in the developing world, where many babies die before their first birthdays. Scientists have found that B.C.G. inoculation reduces infant mortality. In addition to protecting babies from tuberculosis, the vaccine appears to train the immune system to respond to other pathogens, and reduces rates of respiratory illnesses and other diseases.

“The conclusion of our trial — that B.C.G. does not protect health care workers against mild or moderate Covid — is true,” Dr. Curtis said.

But it may still hold promise, he added: “This doesn’t tell us anything about the ability to protect people in other age groups against infections. B.C.G. is still a very important concept in infants.”

Additional analysis of the data collected from inoculated health care workers is continuing. The vaccine’s effects may vary depending on the virus or bacterium it is pitted against, Dr. Curtis said.

The B.C.G. vaccine contains live modified bacteria that have been cultivated in labs around the world for decades, introducing mutations that have led to a number of strains. Differing strains of B.C.G. and varying inoculation regimens may account for inconsistent results in other studies, some experts say.

One of the most successful so far has been a small study of adults with Type 1 diabetes who received multiple B.C.G. inoculations before the pandemic in an effort to improve their blood sugar levels and to reduce infections.

That study found that those who received B.C.G. had far fewer Covid infections than participants who got placebo shots.