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The rationales for and against a third dose of the COVID-19 vaccine

September 9, 2021, 12:00 PM UTC

To booster or not to booster, that is the question facing U.S. public health experts. Last month, the Biden administration announced that all Americans would have access to an additional vaccine dose for COVID-19 by the end of the month. But the declaration was premature, and the CDC and FDA have since split with the White House, saying they need more data before making the decision. (Both agencies still recommend that people who are immunocompromised get a booster shot.)

The question comes as evidence mounts that vaccine effectiveness does wane over time. Studies have shown that antibody levels gradually decline after vaccination, and lower antibody levels are associated with a higher risk of breakthrough infection. Research from the U.S., the U.K., and Israel all show an increase in breakthroughs the more time has passed since vaccination—although the Delta variant, which is more likely to evade antibodies, also played a role in the rise in cases among vaccinated people this summer.

In Israel, the only country to roll out a mass booster initiative for everyone over the age of 12, two recent preprint papers—which have not yet been peer reviewed—show that a third dose of the Pfizer vaccine raises antibody levels and improves protection against infection. Backing up the research, the country appears to have turned the corner on its third wave, and case rates have dropped for the past two weeks.

As Delta continues to wreak havoc in the U.S., boosting people’s immunity with a third shot seems like an easy solution. But the reality is more complicated.

For one thing, while vaccine protection against infection declines over time, by some estimates bottoming out around 50%, protection against hospitalization and death remains high, dipping only slightly from an average of 95% to 85%. Hospital data from the U.S. and Israel bear this out, where the vast majority of beds are taken up by people who are still unvaccinated.

“I think some people, when they hear waning immunity, they think, ‘Oh no, after five or six months, I no longer have any immune protection. The vaccine doesn’t work at all.’ But the data doesn’t say that,” says Jeffrey Morris, a professor of biostatistics at the University of Pennsylvania. “The waning immune protection doesn’t mean it’s gone, it just means that it’s decreased, especially against infection. And when we look against severe disease and hospitalization, we don’t really see much waning there at all.”

As a result, one ongoing debate is whether everyone should get a third dose or only the groups that have the highest risk. An argument in favor of booster shots for all is that, in many ways, immunity is a numbers game. Even if the statistical likelihood of developing severe disease is small, the more people who are infected overall, the more hospitalizations and deaths there will be. By increasing protection against infection during a surge, you will stop the spread of the virus, and in turn limit the number of people with serious illness.

That was the rationale in Israel, where a surge in cases this summer overwhelmed hospitals despite a high vaccination rate. In response, the Israeli Ministry of Health all but mandated a third dose of the Pfizer vaccine for everyone who was eligible—if you didn’t get your booster shot, your vaccine passport expired.

“Israel has been kind of in a crisis with a runaway case burden, which is only now starting to get under control, so they pulled out all the stops,” says Eric Topol, director of the Scripps Research Translational Institute. “We know that if you’re at any age, if you’re vaccinated and you get a breakthrough, you still can transmit to others. The chances are much less than if you were unvaccinated, but to break the chain, they pulled out all the stops. The question is, would we benefit in the U.S. by doing that? And that’s an unknown.”

Instead of offering booster shots to all Americans, Topol suggests limiting eligibility to those who would benefit the most: people who are immunocompromised, over the age of 60, or frontline health care workers.

“I think the booster case is very solid now for people over age 60…and you can also make a pretty strong case for health care workers because they need to be taking care of the sick,” he says. “After that, we don’t really have data yet…but there’s going to be a lesser net benefit of the boosters, most likely, as we go down in age.”

Yair Lewis, an Israeli physician and former member of the country’s COVID-19 advisory team, agrees. Instead of boosting everybody’s antibody levels, he says a third dose should only be offered to the most vulnerable. The rest of the population should be protected through nonpharmaceutical interventions, such as masking, frequent testing, and quarantining after exposure to the virus.

“I think there was close to a consensus that from the way the surge was going on in Israel, it was really important to vaccinate the high-risk populations,” Lewis says. “I definitely supported that. Then there came the issue. ‘Okay, so are we going to boost the entire population?’ And I can speak for myself—I can also tell you that a lot of the colleagues I’ve spoken with think something similar—is that it probably would have been wiser to enforce some sort of light NPI, some nonpharmaceutical interventions.”

One reason for restricting booster shots is the ethical argument that the doses should be saved for countries where vaccination rates are much lower. Another is that resources should still be focused on improving uptake among those who remain unvaccinated. Morris, the UPenn biostatistician, worries that requiring a third dose will dissuade people who are on the fence from getting a vaccine because they’ll interpret it as meaning the vaccines aren’t very effective.

“To get some benefit from just supercharging a little bit of the immune protection that the previously vaccinated already has is nice, but if it comes at the cost of not being able to get more of the unvaccinated to be protected, it could be a net negative,” he says. “Getting even one dose in an unvaccinated person will reduce transmission and risk of serious disease way more than getting a third dose in a previously [vaccinated] person.”

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