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The effectiveness of a vaccine is typically measured by its ability to prevent a specific infectious disease. But in the last several years, researchers have discovered that certain vaccines can also reduce people’s susceptibility to unrelated pathogens. Now researchers are investigating whether these broader beneficial effects can be harnessed to protect people against COVID-19 and pathogens that emerge in the future.

“People always want to think that vaccines . . . just have a specific effect, but that simply isn’t true,” says Katie Flanagan, an infectious disease researcher and clinician at the University of Tasmania who leads a group advising the Australian government on COVID vaccine policy.

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A great deal of evidence for these nonspecific effects comes from decades-long studies that Danish epidemiologist Christine Stabell Benn and her colleagues have been conducting in Guinea-Bissau. When the measles vaccine was first introduced there, the researchers were surprised to see that it reduced child mortality by 70 percent — which was much more than would be anticipated from the vaccine’s ability to prevent measles infection alone. Similar effects were later documented with some vaccines for tuberculosis, smallpox, and polio. But most vaccines didn’t have that broader effect on mortality rates.

Benn’s group showed that the nonspecific benefits came from live vaccines, which contain a pathogen in weakened form, rather than from non-live vaccines, which contain the whole or parts of the dead pathogen. These live vaccines appeared to reduce children’s risk of dying of other infectious diseases, including pneumonia, in addition to protecting against the target pathogen, by stimulating the innate immune system, the body’s first line of defense against pathogens.

Most of the studies to date have been conducted in children, but COVID-19 has offered researchers a chance to see the potential nonspecific benefits of live vaccines in adults. About 30 trials around the world are testing whether live vaccines for other diseases — including a shot for tuberculosis known as BCG, the oral polio vaccine, and the measles, mumps, and rubella shot — also reduce the incidence and severity of COVID-19. One such trial has 30,000 participants.

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“We are going to learn so much from these trials,” Benn says.

Initial findings are coming out: A randomized clinical trial of 301 elderly Greek patients, posted on the MedRxiv preprint server on May 24, concluded that recent BCG revaccination was associated with a 68 percent reduction in the risk of COVID-19 infection. But the study has not been peer-reviewed yet, and other, larger trials are still ongoing.

It’s unclear whether countries that have or used to have widespread BCG vaccination against tuberculosis have fared better than the United States and other countries where those shots have not been widely given. Some studies found that BCG did confer some protection, but others did not. The difference may be due to uncontrolled factors, like widely different health care resources from country to country or the age composition of the population.

There’s currently no indication that the COVID vaccines that are in wide use, such as the ones made by Pfizer, Moderna, and Johnson & Johnson, will confer any nonspecific beneficial effects, though this is something Flanagan and Benn are both eager to study. These vaccines do not contain a live virus.

No one is suggesting that live vaccines for other pathogens are likely to be more effective against COVID-19 than these targeted vaccines are. However, the strategy of using live vaccines to boost overall immunity “has huge potential” for lessening future disease outbreaks before specific vaccines can be developed to fight them, Benn says.

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“We all now realize that this may not be the last pandemic,” she says. “And if we could have some kind of general stopgap vaccination, which could be used in such situations to strengthen immunity, then it would be absolutely a game changer.”

Viviane Callier is a freelance science writer in San Antonio.