Booster shots against COVID-19 are once again on my mind. The U.S. Food and Drug Administration says that older people and immunocompromised people are eligible for a second booster shot provided it has been at least four months since their last shot. After I got over the shock of the FDA calling me “older” — meaning anyone 50 and up — I’ve been pondering whether to get a second booster (otherwise known as a fourth dose of an mRNA vaccine, or third dose of any vaccine if you initially got the Johnson & Johnson vaccine), and if so, when.
Peter, a 60-year-old acquaintance who asked me not to use his last name to protect his privacy, told me he’s going to get a second booster, but not now. He’s holding out for fall and hoping for a variant-specific version of the vaccine. Right now, he and his wife “are vaxxed out,” he says. And he worries that getting boosted too often could hurt his immune system’s ability to respond to new variants. “I just think it’s the law of diminishing returns,” he says.
Lots of scientists and policy makers are thinking about these issues, too. For instance, last week an advisory committee to the U.S. Centers for Disease Control and Prevention met to discuss boosters. And a bevy of studies about how well boosters work and how they affect the immune system have come out in recent weeks, some of them peer-reviewed, some still preliminary.
In making my own decision, I wanted to know several things. First, does a second booster really provide additional protection from the coronavirus beyond what I got from my first booster (SN: 11/8/21)? Second, are there downsides to getting boosted again? And finally, if I’m going to do it, when should that be and which vaccine will I get?
To get a handle on the first question, I need to know how much protection the first booster actually gave me. I’m not immunocompromised, so there’s no reason for me to get an antibody test to see if I have enough of those defenders to fend off the coronavirus. I just have to assume that my immune system is behaving normally and that what’s true for others in my age group also goes for me.
How long does COVID-19 booster immunity last?
Although the exact numbers vary, several studies have found that a third dose of the Pfizer COVID-19 vaccine gave higher levels of protection against the omicron variant than two doses did (SN: 3/1/22). But that protection wanes after a few months.
Data from Israel, where some people have been getting fourth doses for months, suggest that a second booster does indeed bolster protection, but again only temporarily. In health care workers who got a fourth dose, antibody levels shot up above levels achieved after the third jab, researchers reported April 7 in the New England Journal of Medicine. Vaccine effectiveness against infection was 30 percent with the Pfizer shot and 11 percent with Moderna. Both were better at preventing symptomatic disease, with Pfizer weighing in at 43 percent and Moderna at 31 percent. But those who did get infected produced high levels of the virus, suggesting they were contagious to others.
In a separate study published in the same journal, researchers looking at people 60 and older found that a fourth dose gave protection against both infection and severe disease, but the protection against infection began to decline after about five weeks.
There’s more data on protection against severe illness from a study of more than 11,000 people admitted for COVID-19 to a hospital or emergency department in the Kaiser Permanente Southern California health care system. At nine months after the second shot, two doses of the Pfizer vaccine were 31 percent effective at keeping people out of the emergency room with omicron, researchers reported April 22 in Lancet Respiratory Medicine. The shots were 41 percent effective at preventing more severe illness resulting in hospitalizations from the omicron variant.
The third dose (first booster) bumped the effectiveness way up to 85 percent against hospitalization and 77 percent against ER visits, the team found. But the effect was temporary. By three months after the booster, effectiveness had declined to 55 percent against hospitalization and 53 percent against emergency room visits. The same jump in protection and quick waning from the first booster has also been noted in the United Kingdom and Qatar.
It’s been about six months since my first booster shot, so any extra protection I got from it is probably gone by now. But will a fourth dose restore protection?
The CDC calculates that for every million people 50 and older who get a fourth dose of vaccine, 830 hospitalizations, 183 intensive care unit admissions and 85 deaths could be prevented. Those are impressive numbers, but many people think efforts should be focused more on getting still-unvaccinated people immunized instead of worrying about additional shots for the already vaxxed. CDC’s numbers support that. Because unvaccinated people are so vulnerable to the coronavirus, you would need to vaccinate just 135 people aged 50 and older with two shots to prevent one hospitalization. But already vaccinated people still have quite a bit of immunity, so you’d need to vaccinate 1,205 older people with a fourth dose to prevent one hospitalization.
How does my health factor in?
Of course, that’s data concerning populations. I and millions of others are trying to make individual calculations. “People need to make decisions based on their health condition as well as their exposure levels,” says Prakash Nagarkatti, an immunologist at the University of South Carolina School of Medicine Columbia. For instance, people whose jobs or other activities put them in contact with lots of people have higher exposure risks than someone who works at home. People who are older or have underlying health conditions, such as diabetes, obesity, high blood pressure, or lung, kidney, liver and heart diseases are all at higher risk. Those people might benefit from a shot now. “But if you’re 50 to 60 and very healthy, I don’t know if you need it right away,” Nagarkatti says. “You could maybe wait a few months.”
I’ve got some health risks that may make me more likely to get severely ill, and I have a couple of big events coming up this summer where I could get exposed to the virus. So getting boosted now to get a little bump in immunity that should last for a few months seems like a good idea. I’m also basing that decision about when to get a booster on what’s happening with the virus.
Case counts in my county are on the upswing. Nationally, BA.2.12.1, a potentially even wilier subvariant of the already slippery BA.2 omicron variant, is on the rise, making up almost 29 percent of cases in the week ending April 23. South Africa is experiencing a rise in cases caused by the omicron subvariants BA.4 and BA.5. It could be the start of a fifth wave of infection in that country, something researchers thought wouldn’t happen because so many people there were previously infected and vaccinated, Jacob Lemieux, an infectious disease researcher at Massachusetts General Hospital in Boston said April 26 in a news briefing. “It has the flavor of, ‘Here we go, again,’” he said. “So much for the idea of herd immunity.”
Are there any downsides to a second booster?
But would I be harming my immune system if I get a booster shot now? Previous experience with vaccines against other viruses suggests repeated boosting isn’t always a good thing, Galit Alter, codirector of the Harvard University Center for AIDS Research said in the news briefing. For instance, in one HIV vaccine trial, people were boosted six times with the same protein. Each time their antibody levels went up, but the researchers found that the immune system was making nonfunctional, unhelpful antibodies that blocked the action of good ones. So far, that hasn’t happened with the COVID-19 vaccines, but it could be important to space out doses to prevent such a scenario.
Another worry for immunologists is original antigenic sin. That has nothing to do with apples, serpents and gardens. Instead it happens when the immune system sees a virus or portion of the virus for the first time and trains memory cells to make antibodies against the virus. The next time the person encounters the virus or another version of it, instead of adding to the antibody arsenal, it continues to make only those original antibodies.
With the coronavirus, though, “what’s happened is the opposite of antigenic sin,” says Michel Nussenzweig, an immunologist and Howard Hughes Medical Institute investigator at Rockefeller University in New York City. He and colleagues examined what happens to the immune response after a third dose of vaccine, focusing especially on very long-lived immune cells called memory B cells. Those memory cells still made new antibodies when they got a third look at the vaccine, Nussenzweig and colleagues reported April 21 in Nature. That wouldn’t happen if antigenic sin were a problem. And it’s great news since an ever-growing repertoire of antibodies may help defend against future variants.
A separate Nature Immunology study found that other immune cells called T cells also learn new tricks after a booster dose or a breakthrough infection. Those and other studies seem to indicate that getting a booster isn’t bad for my immune system and could help me against future variants.
Is it okay to mix and match COVID-19 booster shots?
Now the question is, which booster to get? Mixing vaccines doesn’t seem to push the immune system toward making the unhelpful antibodies, Alter said. It “tantalizes the immune system with different flavors of vaccines, and seems to reawaken it,” she said. “Even mixing and matching mRNAs may be highly advantageous to the immune system.” She and colleagues found that the Moderna vaccine may make more IgA antibodies, the type that help protect mucous membranes in the nose, mouth and other slick surfaces in the body from infection, than the Pfizer vaccine does. Pfizer’s makes more of the IgM and IgG antibodies that circulate in the blood, data published March 29 in Science Translational Medicine show.
Since I got the Pfizer vaccine for my first three doses, it seems wise to shake things up with Moderna this time. I’ve already booked my shot.
As for Peter, after I laid out the evidence, he said he was convinced that he should probably get a shot now, as his doctor recommends. But he admitted he might just wait to see if Moderna comes out with an updated version of its vaccine.
What’s really needed, all the experts tell me, is to better understand how the immune system operates so researchers can build better vaccines with longer-lasting protection so we won’t be facing needles multiple times per year.
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