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There are now two fully approved COVID vaccines. What does that mean for boosters?

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There are now two fully approved COVID-19 vaccines in the US, after the US Food and Drug Administration granted full approval to Moderna’s COVID-19 vaccine on Monday. Pfizer’s vaccine has had full approval since August. While full approval applies to two doses of either vaccine (boosters or third doses remain available under emergency use authorization), it means the FDA has received the additional safety and effectiveness data it needed to give its final stamp. 

In booster news, extra shots have been recommended to restore protection against the new omicron variant, which has reduced the vaccines’ effectiveness against COVID-19 infection. And new research shows just how well they’re working. 

Two reports published in January by the Centers for Disease Control and Prevention revealed good news about how our boosters are holding up against omicron, and how the vaccines continue to protect against hospitalization caused by COVID-19. When the omicron variant was emerging in the US, adults who received a booster shot were five times less likely to be infected compared to unvaccinated adults. Third doses or boosters of Pfizer or Moderna were also 90% effective at preventing hospitalization with COVID-19 when omicron was emerging, the CDC found.

Everyone aged 12 and older is eligible for a booster. In January, the CDC shortened the period of time someone who got Pfizer’s or Moderna’s vaccine needs to wait for a booster, down to five months instead of six. (People who received Johnson & Johnson’s vaccine should still get a booster at least two months after their one-dose vaccine.) 

The booster recommendation is clear now (get one), but the guidance leaves a little choice up to you. While the CDC recommended that everyone receive a booster dose of Pfizer’s or Moderna’s vaccine — either mRNA vaccine is preferred over Johnson & Johnson’s in most cases, the CDC says, even if you originally got the J&J. That’s because people are now able to “mix and match” COVID-19 vaccines after heterologous booster doses were authorized by the FDA.

While the world continues to watch the coronavirus and scientists adjust information accordingly, here’s what to know about choosing a booster. 

How are the COVID-19 vaccines different? 

While all three vaccines have the same effect — protection against severe COVID-19 disease — the way they function is a little different. Pfizer and Moderna are mRNA vaccines, which teach our cells to make a specific protein and build immunity against a virus. Johnson & Johnson (the only authorized one-dose vaccine) is a viral vector, which uses a harmless virus to activate an immune response that teaches our bodies what to fight in future infections.

Both vaccine types prepare our immune systems for COVID-19 infection and none of the coronavirus vaccines infects us with the actual coronavirus. Pfizer’s and Johnson & Johnson’s booster are the same dose as the original vaccines, while Moderna’s booster is half the size of its original vaccine. 

After an outside committee that advises the CDC raised concerns over a rare but sometimes fatal blood-clotting disorder that can happen following vaccination with Johnson & Johnson’s vaccine, the CDC recommends people receive Pfizer’s or Moderna’s vaccine or booster instead. However, Johnson & Johnson’s vaccine is still authorized and available for people age 18 and up if they prefer it. 

Does mixing and matching work?

Research available now in the US as well as other countries shows that choosing a different COVID-19 vaccine as a booster is effective. In some cases, mixing and matching seems to produce a stronger response compared with sticking to the original vaccine. 

During a mix-and-match COVID-19 vaccine trial funded by the National Institute of Allergy and Infectious Diseases (before omicron was the dominant variant), boosters from all three vaccine companies induced good immune responses in roughly 450 people who got different vaccines. In the study, Moderna’s booster gave the most robust response. However, that study examined a full dose of Moderna, rather than the authorized half-dose of the company’s booster, which could minimize Moderna’s edge over Pfizer, as The Atlantic reported. 

Another preliminary study of 64 people found that people who originally received Pfizer’s vaccine, but then got a booster of Johnson & Johnson’s vaccine, had a stronger response to Johnson & Johnson’s vaccine. This included the harder-to-measure T-cell immune responses Johnson & Johnson’s vaccine appears to protect with as opposed to antibody response alone — which Johnson & Johnson said may be the reason two doses of its vaccine give great protection against hospitalization and disease caused by the omicron variant.

An earlier study from Spain published in the Nature journal in May 2021 found that mixing one dose of AstraZeneca (a similar vaccine to Johnson & Johnson’s) with one dose of Pfizer produces a higher antibody response than people who receive two doses of AstraZeneca. It isn’t clear whether this group had a higher immune response than people who received two doses of Pfizer, however.

Which booster shot should I get? 

No matter which COVID-19 vaccine you originally got (Pfizer, Moderna or Johnson & Johnson), you should get a booster of Moderna’s or Pfizer’s vaccine, the CDC says. Kids and teens ages 12 to 17 should get a Pfizer booster, however, because Pfizer is the only COVID-19 vaccine authorized for people under age 18. 

The preference for either mRNA vaccine followed concerns of a rare but serious blood-clotting disorder associated with Johnson & Johnson’s vaccine, called thrombosis with thrombocytopenia syndrome. Since the CDC paused the distribution of the disorder to investigate, more information revealed that it’s less rare than previously understood and occurs in both men and women. (Although still rare overall, occurring in 57 cases out of 16.9 million doses of Johnson & Johnson given, per the CDC, women ages 30 to 49 are at higher risk of the disorder with about 1 out of 100,000 women experiencing it.) Nine people have died from TTS and all cases required hospitalization or ICU admission, according to a CDC presentation. 

Johnson & Johnson’s vaccine is available to you if you prefer it for any reason, or if you can’t take Moderna’s or Pfizer’s because of an allergy. But given the excellent safety and wide availability of Pfizer’s and Moderna’s vaccine, the CDC made the recommendation in line with what other countries have done for AstraZeneca’s vaccine, which is associated with the same rare issue. 

A study published by the CDC in September (before omicron) compared vaccine effectiveness in the real world found that two doses of Moderna’s vaccine was 93% effective at preventing hospitalization, two doses of Pfizer were 88% effective and one dose of Johnson & Johnson was 71% effective. And while omicron does evade our protection against COVID-19 infection given by the vaccines, some protection against severe disease remains. 

According to data on booster doses collected by the CDC, most people who got Pfizer’s or Moderna’s vaccine seem to stick to their original vaccine brand (most people who got Johnson & Johnson’s vaccine originally have gotten a different booster). However, millions of Americans have opted for a different vaccine brand as a booster, and no safety concerns have been raised by either the FDA or CDC in people who’ve mixed and matched. 

Are you fully vaccinated after your booster? 

Importantly, the definition of fully vaccinated hasn’t changed (though it might in the future). You’re still fully vaccinated two weeks after your second Pfizer or Moderna shot or two weeks after your Johnson & Johnson vaccine. Whether someone has received a booster doesn’t affect their “fully vaccinated” status. 

Can I mix and match the first two shots?

No, the CDC’s statement on mixing COVID-19 vaccines only applies to boosters. As of now, the FDA has only authorized a mixed-series booster, meaning the first coronavirus vaccine series must be one dose of Johnson & Johnson or two doses of Moderna or Pfizer. 

Once the mixed-series boosters start rolling out to Americans in greater numbers, there will be more data on the safety and effectiveness of a mixed COVID-19 series. Although it might be too early to hope, this might mean that data on mixing for boosters will inform decisions on primary coronavirus vaccine series being used together, making it easier to reach underserved communities, and possibly reducing health care and vaccine inequity.

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