Is it possible to overdo it with COVID-19 vaccine boosters? What is and isn’t known

First, it was one or two COVID-19 vaccine shots. Then it was get a booster shot after eight months, until they changed it to six, then five months. Now, federal health authorities have approved yet another shot four months from your last one if you’re at least 50 or in poor health.

But is it possible to overdo it on COVID-19 vaccine boosters? Could it end up like the overuse of antibiotics that medical experts now warn is breeding superbugs resistant to them?

There’s no evidence of that yet, most experts say. But the boosting-too-much questions are fueling a growing debate among scientists as an expert panel meets April 6 to advise the Food and Drug Administration on vaccine booster doses and updates tailored to emerging variants.

Early this year, the European Medicines Agency’s Head of Vaccines Strategy, Marco Cavaleri, raised the concern that excess boosting could weaken rather than strengthen our immunity.

“If we have a strategy in which we give boosters every four months, we will end up potentially having problems with immune response,” Cavaleri said at a Jan. 11 news briefings.

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Dr. Sarah Fortune, a professor at the Harvard TH Chan School of Public Health Department of Immunology and Infectious Diseases, told the German news organization Deutsche Welle a week later that Cavaleri likely was referring to possible exhaustion of the T cells that help protect the body from infection.

“T cells become dysfunctional when they repeatedly see antigen in certain contexts,” Fortune told Deutsche Welle. Vaccines introduce antigens to generate an immune response. But Fortune added that the studies on T cell exhaustion are based on HIV or cancer patients “where the antigen is there all the time, not just repeated vaccination.”

So far, there’s been no indication that repeated vaccination weakens immunity or produces resistant viral strains.

“I haven’t seen any evidence to suggest that additional boosting would weaken protection or breed variants,” said Holden T. Maecker, director of the Human Immune Monitoring Center at the Stanford University School of Medicine. “Our knowledge from immunology generally suggests no such weakening or overload, as long as immunizations are sufficiently separated in time.”

But others noted that much remains unclear.

“We really don’t know honestly,” said Dr. Michael Daignault, an emergency physician at Providence Saint Joseph Medical Center in Burbank, who noted that the United States is relying on data from the second-booster program that Israel just started in January . “I know there’s a lot of speculation, but there’s no data on over-boosting.”

The COVID-19 vaccine booster intervals US health officials are calling for having little precedent in public health. Many childhood immunizations are given in two to four shots from birth to six years of age. But apart from tetanus boosters every 10 years, they’re done after that. Flu shots are given annually, tailored to the prevailing strain around the world.

But it’s unclear whether some number of COVID-19 vaccine shots will deliver lasting protection, or whether it will require repeated boosting, and if so, how often? Cavaleri and other health officials have argued boosting multiple times a year is impractical and that vaccination efforts should focus on preventing severe illness rather than reducing mild “breakthrough” cases among the immunized.

Others like Dr. Bob Wachter, who chairs the medical department at UC San Francisco, have countered “there’s a small but real risk” that a breakthrough case will lead to chronic “long COVID” illness and raise long-term risk of mental illness, cognitive decline and diabetes. He called the risk of getting over-boosted “theoretical” and urged those eligible for the second booster to “get the shot.”

Is there a danger overuse could weaken the vaccines’ effectiveness like with antibiotics?

There’s no comparison to overuse of antibiotics, said Dr. Robert Quigley, an immunologist and cardiac surgeon in Pennsylvania who is the global medical director for International SOS, a firm that advises companies whose employees face medical issues traveling internationally.

“We’re talking apples and oranges,” Quigley said. “You can’t extrapolate from the antibiotics to vaccines. The mechanisms of action are so unrelated and involve different fundamental scientific principles from one to the other.”

Antibiotics kill or suppress growth of infectious bacteria, while vaccines use neutralized elements of disease-causing bacteria or viruses to trigger an immune response from your body.

Is there a benefit in waiting longer between boosters? The Centers for Disease Control and Prevention recently revised its guidance for the interval between the first two Pfizer and Moderna shots, based on experiences in Canada and the United Kingdom that a longer interval between the shots improved their effectiveness in preventing disease and reducing side effects.

But the CDC said the benefits peaked at eight weeks between shots — which Daignault noted is significantly less than the recommended four-month second booster interval.

Maecker said the booster intervals were based on evidence of gaining immunity.

“I would say there’s no reason to boost sooner than four to six months, just because there’s no real benefit to a fully vaccinated person — immunity doesn’t wane that quickly,” Maecker said. “So to me, less than four months would be too soon. I think as long as people are not trying to boost too soon, the risk-benefit ratio is very favorable. I’m getting my boost on Sunday!”

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