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3 reasons you probably don't need a 4th COVID shot any time soon, according to experts

Mar 22, 2022, 04:13 IST
Business Insider
30-year-old Ivonn Cruz getting a dose of COVID-19 vaccine in Los Angeles on January 29, 2022.Francine Orr / Los Angeles Times via Getty Images
  • Pfizer and Moderna have asked the FDA to allow adults in the US to get 4th dose boosters.
  • Experts say boosting with the same shots again may not be the best strategy for this virus.
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Both Pfizer and Moderna are asking the US government to give the go-ahead for fourth doses of their COVID-19 vaccines.

Last Tuesday, Pfizer announced it had submitted an application to the US Food and Drug Administration "for Emergency Use Authorization (EUA) of an additional booster dose for adults 65 years of age and older."

That was after Pfizer's CEO Albert Bourla told CBS over the weekend that Americans should prepare to get COVID-19 boosters every year, like what happens when people line up for fresh flu shots each fall.

"Right now, the protection we are getting from a third is good enough, actually quite good for hospitalizations and deaths," Bourla said, while also stressing his concern that "the duration of the protection doesn't last very long."

By Thursday evening, Moderna, too, said it had submitted an EUA to the FDA for fourth doses of its COVID-19 vaccine. Moderna's request is broader than Pfizer's. According to the company, the EUA would allow fourth doses to be given to all adults, letting healthcare providers "determine the appropriate use" of boosts among their patients, by weighing factors including a person's age and comorbidities.

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However, independent infectious disease experts, including some who advise the FDA on vaccines, told Insider that the move to give people in the US fourth shots might not be the most prudent idea, for at least three key reasons.

Here's a quick look at the latest research, and independent expert opinions on whether fourth doses are right for you.

1: The virus has changed. The vaccines haven't yet.

A COVID-19 vaccine booster ad in the New York City subway on January 9, 2022.Michael Nagle/Xinhua via Getty Images

The vaccines on offer now from both Moderna and Pfizer are still the original formulations, meaning they're not tailored to the COVID-19 variants which are circulating, like Omicron, and the fast-spreading Omicron subvariant, BA.2.

All the vaccines we currently have were developed based on virus that was sequenced in Wuhan in January of 2020. In the two-plus years since then, the virus has moved on, but the vaccines have not.

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"I personally don't think that the pharmaceutical companies should be talking about boosts with the same vaccines that we have," Dr. James Hildreth, a leading infectious disease expert who advises the FDA on vaccines, told Insider. "I would much prefer the focus being on looking at the sequences that have come out from the variants that we've dealt with, and try to do a vaccine that would offer protection against those, as opposed to just giving people a fourth shot.

Hildreth is worried that by continuing to use shots that are tailored to a 2-year-old virus, we might create some new problems. Boosting with an out-of-date shot could produce antibodies that have little value against circulating viral strains. Or, as the virus evolves, there's also the possibility that it could learn to develop better resistance to the vaccines. More frequent boosts tailored to an older version of the virus could speed along that process.

"I hate to even bring this up, but there's evidence from studies in mice that repeated immunizations, with the intervals too short, you can actually start to induce tolerance," Hildreth said. "And that's the last thing you want."

One big problem with modifying the existing vaccines, though, is that it's still unclear what kind of FDA review a variant-tailored mRNA vaccine would require before it could be given out. In addition to variant-specific boosts, several independent research groups and pharmaceutical companies are also working on pan-coronavirus vaccines that would target different coronavirus strains at once, hoping to achieve broad immune protection against future coronaviruses that aren't even in circulation yet, in addition to those that are spreading now. Those pan-coronavirus vaccines are still at least a few years away, at best.

2: We haven't actually seen any good data that 4th dose boosts are necessary, or all that helpful, for most people

The data we have on boosters so far only suggests that older people, as well as those with underlying medical conditions, will derive good benefits from fourth doses. There isn't great data that shows additional booster shots benefit younger, intact immune systems, when it comes to preventing severe disease.

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A recent CDC study suggested that vaccine effectiveness against severe outcomes including mechanical ventilation and death during the peak of the Omicron wave in early January was 88% with two shots, and 94% with three, suggesting a booster shot provides only marginal improvement in vaccine effectiveness, for most people. Another CDC study showed more than 96% of fully vaccinated people who were hospitalized with COVID during Omicron had preconditions, and the same was true in 9 out of 10 of boosted adults hospitalized with Omicron.

Even Moderna executives agree that additional booster programs, at this point, should be largely focused on the most vulnerable patients.

Moderna President Stephen Hoge told Insider last week that "for those who have cancer, COVID can actually be a life-threatening disease, even post-vaccination," but he said additional boosts aren't necessarily needed for members of the general public under 65, without preconditions.

3: Fourth doses are only providing marginal benefits so far

Israel has already tried out fourth doses of Pfizer and Moderna's vaccines on young, healthy populations, and only gotten mediocre results. One study of more than 1,000 Israeli healthcare workers who were given fourth shots four months after their initial boost, suggested there was no additional boost to the immune system with a fourth dose, beyond the protection achieved with three doses. While a fourth dose temporarily increased antibody levels to where they were after a third shot, there was only a "marginal" temporary benefit to giving young, healthy populations another jab.

"We have vaccines right now that do provide protection from severe disease," Dr. Barney Graham, one of the co-inventors of Moderna's COVID-19 vaccine at the National Institutes of Health, told Insider, saying the vaccines are "working more like we expected" at this point, and that mild COVID-19 infections in young, healthy people who've been vaccinated are not necessarily major cause for concern going forward.

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"That's actually part of how the vaccines work — you protect the lower airway, and upper airway exposures that cause very mild or no disease will boost the responses, and keep you immune," he said.

A recent study of more than 422,000 people across the US who took Johnson and Johnson's much maligned single-shot vaccine, likewise, suggested that it has been working quite well at preventing hospitalizations and deaths, though that finding was slightly less true among the most vulnerable patients, and in older adults.

"Let's identify those who are most vulnerable and most susceptible to severe disease, hospitalization, and possibly dying, and make sure we make every effort to get them protected," Hildreth said.

Boosting the US while ignoring the places where new variants might emerge is not an expert-backed strategy

Rather than considering fourth doses for large swaths of those who are already vaccinated in the US this summer, Graham says more shots should be sent to the bottom half of the globe. He's worried that COVID-19 could spread fast there, as temperatures tumble, and that may give rise to a concerning new variant that could "more fully escape all of our current vaccines and monoclonal antibodies."

"Can we please just get the Southern Hemisphere vaccinated before June?" he said. "We have things that do work, at least to protect against severe disease, and the question is: are we going to deploy them in the place where it could help the most?"

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"In general, the reason we have had to deal with variants at all is because we didn't get the world immunized fast enough," Graham added.

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