7 questions about Covid-19 booster shots, answered

Will you need a booster? Does it matter if you got Pfizer, Moderna, J&J, or another vaccine?

If you’ve gotten vaccinated against Covid-19, you may have experienced the giddy rush that comes with knowing you’ve now got increased immunity. It feels like a superpower! You can do some normal things again!

But you may also be starting to wonder what’s next. Will you need a booster shot in a few months? Does the answer differ depending on which vaccine you originally got? Will we all be getting annual boosters that are tailored to fight new variants, just like we get flu shots each winter that are tailored to fight new strains?

According to a study recently published in Nature, people who received mRNA vaccines — Pfizer/BioNTech or Moderna — may have such lasting immunity that they won’t need boosters for years. That’s great news, although it also leaves some of us asking new questions: Does that still apply to me if I’m elderly or immunocompromised? And what if I got a different type of vaccine, like Johnson & Johnson or Oxford/AstraZeneca?

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Some scientists who got the one-and-done J&J vaccine have said they’re now topping up with an extra shot of Pfizer or Moderna, out of concern that their one dose won’t be enough to stop the more contagious delta variant. Naturally, people will wonder if they should follow suit.

But so far, the Centers for Disease Control and Prevention hasn’t offered any recommendations on this. A working group for the CDC said in June there isn’t yet evidence to suggest that a booster is needed. National Institute of Allergy and Infectious Diseases Director Anthony Fauci likewise said there isn’t enough data for the government to recommend a booster for J&J recipients.

So here’s a guide to navigating our collective confusion about boosters. These answers to common questions are based on what experts currently know, though of course they might shift as new data comes to light.

1) What are boosters and how do they work?

A booster shot is a way to strengthen your immune system’s response to a pathogen. What goes into the booster can be the exact same as your original vaccine, in which case its goal is to increase the magnitude of protection (for example, by producing more antibodies). But scientists can also tweak what goes into the booster if they’re aiming to protect you from a new variant — a version of the virus that’s mutated significantly from the original version you were vaccinated against.

To understand this more clearly, it helps to review some basics about how our bodies mount an immune response to a virus. It’s not just antibodies that save us (though those obviously help). There’s a whole lot more our immune systems have to offer, as Vox’s Brian Resnick and Umair Irfan have explained:

There are killer T-cells, which hunt down and kill cells that have been infected. There are helper T-cells, which stimulate killer T-cells and recruit yet another class of cells called macrophages to gobble up infected cells, and they also stimulate B-cells, which … are critically important because they produce antibodies.

Certain types of B-cells — recall, these are the ones that make antibodies — become memory B-cells. These save the instructions for producing a particular antibody, but they aren’t active. Instead, they hide out — in your spleen, in your lymph nodes, perhaps at the original site of your infection — waiting for a signal to start producing antibodies again.

When you get a booster shot, it gives your memory B-cells that crucial signal to reengage. This can be useful whether the booster contains the original vaccine recipe or something different. If it contains the original recipe, it’ll amplify the signal, increasing the number of antibodies produced. If it contains a tweaked recipe, it’ll retrain the cells to recognize new features of the virus and produce antibodies, should you be exposed to the variant.

2) Which groups will need a booster shot for Covid-19?

A booster only applies to people who have been vaccinated, so that’s the first bar to clear.

Over the coming months, health authorities will be considering two other factors to figure out if you’d do well to get a booster shot.

First, are you a relatively young and healthy person who likely mounted a robust response to the vaccine, or are you an elderly or immunocompromised person who may not have mounted such a robust response? Boosters are much more important for the latter group to consider.

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Second, is there a new variant that’s different enough from the original virus that it can sneak past the immunization you’ve already got?

“In the second scenario, you’d need a booster for everyone. That’s my prediction,” said Ali Ellebedy, an immunologist at Washington University in St. Louis who co-authored the new Nature study. In other words, if a new variant were to emerge that’s radically different from what we’ve seen to date, we’d want to achieve a high level of booster uptake across the population — effectively starting the mass vaccination campaign all over again. “But if we control the variants, then maybe we don’t need it for all of us, but we need it for that special population” who are immunocompromised or elderly, Ellebedy said.

In fact, the UK — which has approved all three vaccines that the US is using, plus the vaccine developed by Oxford/AstraZeneca — is already planning to give out boosters to those age 50 and over before the winter.

Krutika Kuppalli, an infectious disease expert at the Medical University of South Carolina, said we should expect to see potential booster shots rolled out to priority groups first, just like with the original vaccines. “I think you will have to have a targeted approach towards how you roll them out due to a supply/demand consideration,” she said. “I would envision rolling them out to those who are most immunocompromised first,” like transplant recipients and cancer patients.

3) Are you more likely to need a booster if you got J&J or Oxford/AstraZeneca than if you got Pfizer or Moderna?

This is tricky.

Ellebedy’s study indicates that most people who’ve gotten an mRNA vaccine like Pfizer or Moderna may not need boosters for years. The research team took samples from participants’ lymph nodes — where immune cells train, in a structure called the germinal center, to recognize new pathogens. Nearly four months after the participants got their first Pfizer or Moderna dose, the germinal center was still hard at work and the number of memory cells hadn’t dropped. It was a great sign.

The team did not look at the J&J vaccine. (Note that, per the study’s “competing interests” section, some of the authors are consulting for Pfizer or serving on the scientific advisory board of Moderna.) But in an interview with the New York Times, Ellebedy suggested that J&J may not stave off the need for boosters as well as the mRNAs do.

Monica Gandhi, a physician and medical professor at the University of California San Francisco, questioned that. “I don’t see any reason why J&J or AstraZeneca would not produce the same strong immune response,” she said. “The study author said the J&J vaccine will probably not do this. I thought that was completely not indicated [by the science]. I couldn’t believe it.”

When asked to clarify, Ellebedy told me it’s not that he thinks the mRNA vaccines produce a more durable response. Instead, it’s about quantity — the number of antibodies produced and the number of cells that the body commits to becoming memory cells.

“There is a quantitative difference in the number of antibodies that are generated after two doses of the mRNA vaccine — it’s higher than those produced by one dose of J&J. That is also evident in terms of the efficacy in trials,” Ellebedy said. Whereas the mRNA vaccines boasted 94 or 95 percent efficacy in preventing symptomatic Covid-19, J&J’s efficacy rate was 66 percent in clinical trials. (All three were highly effective at preventing hospitalization and death from Covid-19.)

Given this, Ellebedy said, “I think potentially it should be considered for those who received one dose of the J&J vaccine to get a booster immunization, especially with one of the mRNA vaccines.”

But J&J said on July 1 that a booster or second dose of its vaccine is not necessary. In a press release, the company said it had conducted a small study showing that a single dose of J&J provides adequate protection against the delta variant. The results have yet to appear in a peer-reviewed journal, but they are encouraging: Not only did one dose elicit a robust antibody response against the variant, but the antibodies also increased over time. Nevertheless, the company is testing to see whether giving two doses will provide even better protection.

In the meantime, some experts, like Peter Hotez from Baylor College of Medicine, say J&J recipients in the US should wait for guidance, particularly since rates in the country are currently low.

But other scientists, concerned about the spread of the delta variant, have already topped up with Pfizer or Moderna, reasoning that it certainly can’t hurt and may well help. Angela Rasmussen, a virologist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization, in Canada, recently got a dose of Pfizer after receiving J&J in April.

On Twitter, she urged Americans who received J&J to ask their doctors about possibly getting a second shot, noting that some doses of mRNA vaccines may otherwise go unused: “If you live in a community with overall low vaccination, I’d suggest you strongly consider doing so.”

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In any case, the takeaway for now seems to be that there’s no need for J&J recipients to be concerned about not having gotten an mRNA vaccine as a first dose.

“I don’t think people who got a different vaccine should feel cheated,” said Kuppalli, the infectious disease expert. “The J&J and AstraZeneca vaccines are both very good and for the most part have good protection against Covid (minus AstraZeneca against the beta variant). The most important thing to remember is that the vaccines have been effective at preventing Covid-19-related hospitalization and death.”

4) Is it important for your booster shot to match the original vaccine you got? Or can you mix and match?

Your booster shot, if you get one, does not need to match your original vaccine.

“Not at all does it need to be the same!” said Gandhi. “In fact, there’s recent data that mixing and matching probably boosts the immune response. There will be likely no looking at type or brand in future.”

People who got a shot of the Oxford/AstraZeneca vaccine and then got a Pfizer shot a month later produced stronger immune responses than people who got two Oxford/AstraZeneca doses, according to a not-yet-peer-reviewed study. The mix-and-match strategy produced an antibody level similar to that from two Pfizer doses. Impressively, combining the two vaccines also created the strongest T-cell response — more than double that from two Pfizer doses.

There are already several studies showing the benefits of mixing and matching vaccines, and so far they haven’t reported severe adverse effects. That said, the studies have been fairly small — too small to pick up adverse effects if they occur rarely — so some scientists say we still need larger studies.

5) What are the odds that we’ll be getting a variant-tailored annual booster, similar to the annual flu shot?

An annual Covid-19 booster shot is not likely. That’s because Covid-19 is very different from other infectious diseases like the flu. The flu has a rapid mutation rate, meaning it changes a lot from year to year. Although the virus that causes Covid-19 has developed some mutations along its spike protein, the changes haven’t been so massive that we’re likely to need a variant-specific booster every year.

“Assuming there’s no crazy variants, meaning there’s nothing really completely different, I don’t see why anyone with a healthy response to the vaccine would need a booster in the next two to three years,” Ellebedy said.

Gandhi is even more optimistic. “It’s very unclear if people who are immuno-competent are going to need boosters at all,” as long as they have been fully vaccinated, she said.

That’s because all of the vaccines induce such a good immune response — which, again, includes not just antibodies but also T-cells and memory B-cells. Gandhi cited a 2008 study that showed that people who’d been infected with influenza as kids way back in 1918 still had strong memory B-cell immunity — 90 years later. Clearly, memory B-cells can last several decades.

But to be on the safe side with Covid-19, and because the novel coronavirus is still so new, Gandhi thinks it makes sense to give out boosters once a decade. “I think that a prudent course would be once every 10 years,” she said. “Definitely not yearly, definitely not soon.”

Remember, though, that this is assuming no radically different variants emerge. We can’t predict what variants will arise from this virus, and low vaccination rates globally increase the chances of variants developing. If you’re vaccinated, your chances are good against variants, but this virus has certainly surprised us before and may surprise us again.

So experts will be engaged in population-level surveillance and monitoring of vaccine trial participants over the coming months and years. If they start to see vaccinated people getting breakthrough infections at a higher-than-expected rate, that’ll be a canary in the coal mine indicating it may be time to think about boosters.

6) With boosters, is more always better? Could you potentially get multiple boosters, or do additional ones risk diminishing returns?

“There is no scientific reason to think that having additional boosters would be detrimental in any way,” Ellebedy said. “We have studies from the UK showing that even a third dose of AstraZeneca was helpful. The worse-case scenario is that this dose doesn’t add anything, but there’s no reason to think it would harm us.”

That said, experts don’t think everyone will be offered multiple free boosters, nor should they be. “It’s just simply not going to be done,” Gandhi said. “It’s not indicated [by the science]. It’s expensive and insurance companies won’t pay for it. I guess people could go and pay for it out of pocket, but it really does need to be based on indicatedness and not anxiety.”

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Gandhi said we should remember that although boosters increase antibody levels (“that’s sort of a duh moment — like, of course!”) that doesn’t mean we need those higher levels in order to be protected. “T-cells are there, memory B-cells are there, so if they see the pathogen in the future they’ll just come out and fight that pathogen. There’s no reason to get boosters just to boost your antibodies temporarily.”

In fact, developed countries clamoring for boosters could distract from the need to provide first and second vaccine doses to developing countries. Which brings us to …

7) How should we think about booster supply in the US when there’s still a massive shortfall of vaccines in developing countries?

“I think if we want to focus on global vaccine equity when it comes to Covid-19, we need to try and get everyone at least one dose of the Covid-19 vaccine before we start producing boosters that will benefit individuals in resource-rich countries,” Kuppalli said. “As it is, we have front-line and health care workers in parts of the world who have not been able to get access to the Covid-19 vaccine, who should get vaccinated before we even begin talking about boosting individuals who have been fully vaccinated.”

If the concern is that people who are vaccinated may have waning immunity, she added, then it would be important for them to continue using precautionary measures like masks and social distancing to protect themselves, as governments work on providing vaccines to people who haven’t even had the chance to be vaccinated in the first place.

To decrease the likelihood of new variants popping up that might necessitate boosters and precautionary measures, we need to remember that we’re in the midst of a global fight against the virus.