Booster shots are being rolled out across much of the world to boost protection against COVID-19, raising questions about when exactly they should be given. While there are no clear-cut answers, doctors say there’s a downside to getting them too soon.
The immune system needs time to build up its defenses. After vaccination or a natural infection, the cells in the lymph nodes begin to mature and improve so that they are better prepared if they encounter the pathogen again. It takes several months to build up what’s known as immune memory — essentially protection galvanized by long-lived, antibody-secreting plasma cells residing in niches like the bone marrow.
A booster shot given several months after the immune system is primed by an initial series — usually two doses of the vaccine — can amplify its response, said Stanley Plotkin, a veteran vaccinologist and professor emeritus of pediatrics at the University of Pennsylvania in Philadelphia. The additional inoculation triggers a surge in antibodies that are better at antagonizing a range of SARS-CoV-2 variants, he said.
“That interval could be as short as four months, but in general, a six-month interval is probably best,” said Plotkin, whose pioneering research more than 50 years ago led to a rubella vaccine.
An even shorter interval, such as two months, could compromise the body’s ability to mount a sustained immune response, he said in an interview.
That’s because the immune system takes time to rejuvenate after it quickly and rudely makes antibodies against a new enemy, said John Wherry, director of the institute of immunology at the university’s Perelman School of Medicine. As the “emergency response” wears off, the body works to make better antibodies that can be boosted quickly when stimulated by a new dose of vaccine or a natural infection.
“A little rest seems to improve ‘boost’,” Wherry said.
So-called neutralizing antibodies that attach to coronavirus particles and prevent them from entering healthy cells are critical in the defense against COVID-19. However, they decline months after immunization or natural infection, increasing the risk of SARS-CoV-2 infection. That has prompted health authorities to recommend an additional shot to adults to boost their protection against a wintry COVID-19 wave fueled by the hyperinfectious delta strain.
Researchers at Chicago’s Northwestern University found that a third dose of either the Pfizer Inc. either Moderna Inc. which about eight months after the second dose was shot, led to a 25-fold increase in antibody levels in a study of 33 healthy adult volunteers.
There is some evidence that even longer intervals may be helpful, said Miles Davenport, head of the infection analysis program at the Kirby Institute at the University of New South Wales in Sydney. Longer delays between doses of AstraZeneca Plc injection and vaccinating COVID-19 survivors at different times show that the maximum immune response can come if a boost is given at least a year after the second dose, he said.
Six months is “arbitrary” for a third dose and may represent a trade-off between achieving maximum protection and reducing the immediate risk of infection, he said.
“If you get the third dose, I’d say will probably depend on how much virus is circulating,” he said. “And if there are a lot of viruses circulating, you’re probably willing to compromise on your maximum response to get protection faster.”
Timing should also be informed by which vaccine was used for the first two doses, Davenport said. For example, antibody levels will drop to lower levels if AstraZeneca was used as the primary treatment than if Moderna was used.
Studies from Israel, one of the first countries to offer booster shots, indicate that a third injection restores the effectiveness of vaccines, increasing protection against hospitalization and severe illness from COVID-19 to more than 92 percent.
“What we don’t know at this point is how long the response will be after that third dose,” Plotkin said. It may be necessary to give booster doses periodically, especially to seniors, to ward off COVID-19 epidemics, he said.
“I don’t know if it will be every year, but I doubt it will be satisfying to just let things go unless we are willing to continue the diseases at a rapid pace,” the 89-year-old doctor said.
The poorer immune response to COVID-19 vaccination and the increased risk of dying from SARS-CoV-2 infection in the elderly may necessitate a different immunization approach for them, he said.
Yearly shots probably won’t be necessary for most people in the long run, said Davenport of the University of New South Wales. “We’re going to get our annual boost from exposure to circulating virus,” he said.
“I hope if you get a third dose it keeps your protection high long enough that you can be exposed to infection and strengthened by infection while still being pretty well protected,” he said. “We’re trying to collect the evidence for that from the literature.”
Story of Jason Gale.