Will You Need a Covid-19 Booster Shot?
A vaccine reporter distills what we know now, how boosters work, and some (fun) lessons in immunology
A lot of articles and discussions have been popping up on the topic of booster shots for Covid-19 vaccines: Will we need them? Why will we need them? When will we need them? I’ve noticed an unsettling trend among the articles I’ve been reading about boosters. Many suggest we’re almost certainly going to need booster shots, but none provide actual data to support that claim. The articles are highly speculative.
The reality is that we won’t know if we need boosters at all until we have data in hand telling us we need them. But I’ll explain what that means and why I’m skeptical of articles claiming we’ll “probably” or “likely” need boosters “by fall” or “by the holidays.”
If you don’t want to read this whole article (and my fun analogies designed to simplify immunology), here’s a quick summary:
- The Pfizer, Moderna, and Johnson & Johnson CEOs have all at some point publicly said they think boosters will be needed. They also have a vested financial interest in saying so. (It doesn’t mean they’re wrong — we just don’t know yet.)
- Some infectious disease experts say we’ll likely/probably/definitely maybe need a booster. Again, we don’t have data yet to say one way or the other if that’s the case. It’s all speculation at this point.
- We’ll know we need boosters when Covid-19 cases begin increasing in clinical trial participants and other fully vaccinated people. If we start seeing more cases, that means the vaccine’s protection is wearing off, and a booster may be needed.
- We’ll know if we need a newly formulated vaccine specifically for the variants if we start seeing more severe Covid-19 cases from the variants in fully vaccinated people.
- Pfizer, Moderna, and J&J are preparing for both those scenarios. Pfizer and Moderna have already begun phase 1 trials for one or both possibilities.
- Anthony Fauci said we’ll probably know by the fall whether we’ll need boosters. He seemed to be basing that on the expectation that we’ll have data showing whether and how much antibodies have begun dropping off in trial participants. But again, we really won’t know we need a booster unless or until we have data saying so.
- Bottom line: Will we need boosters? No one really knows yet.
How booster shots work
A booster shot is an extra dose of a vaccine that strengthens your immune response against the pathogen. However, several articles about boosters are conflating two different ideas — true booster shots and newly formulated vaccines to address the variants. So let’s clarify the difference first, with a refresher on how vaccines work.
The Pfizer and Moderna vaccines currently require two doses, and the J&J vaccine requires one. The first and second doses of the mRNA vaccines are identical. There’s no difference between the first dose and the second dose. What’s different is your immune system’s response to the second dose: it’s stronger.
Think of a vaccine as mimicking an intruder on a military base. Your immune system is the unit guarding the base (your body). The truly dangerous intruder would be the virus, but a vaccine is just dressed up like the virus to trick the soldiers into responding, like an unannounced training drill. (If we want to be precise, the Covid-19 vaccines tell your cells to create a bunch of harmless particles that look like the real virus because they’re wearing the enemy’s uniform — the spike protein.)
The first time the vaccine-disguised-as-a-virus comes around, the sentries on duty spot it (or, more precisely, spot the enemy’s uniform) and sound the alarm. Generals (T cells) notify their colonels (B cells) to bring in the grunts (antibodies) and train them to attack this specific virus (which isn’t the real virus, but they don’t know that). The immune system is pretty damn efficient, so that training (B cell production of antibodies) only takes a week or two before the troops have neutralized the threat. And now a battalion of soldiers (antibodies) are ready to move fast if they see that intruder again.
When you get the second dose, lo and behold, here’s that same enemy again! (Again, the fake one, wearing the spike protein uniform.) The soldiers waste no time. They are ON IT. And the colonels, noting that the supposed combatants have come around again and may become a regular threat, train yet more grunts to recognize and attack the enemy.
But then that’s that. The enemy doesn’t come around again (or if it does, in the form of the real virus, the soldiers act so quickly that it’s dispatched before it has a chance to cause symptoms). And over time… the soldiers let their guard down. Time passes… soldiers leave the army… the number of troops that once knew how to attack SARS-CoV-2 when they saw the spike protein begins to dwindle… until there may not be enough of them left to effectively destroy the real virus if it comes by.
A booster shot is an additional dose of the vaccine to whip those soldiers back into fighting mode. It’s an extra training drill to ensure they aren’t resting on their laurels and that the new recruits know what to do.
However, what if the enemy that comes around next time looks a little different (a variant)? Its uniform is similar, but not identical (mutations in the spike protein). And its fighting tactics (ability to evade the immune system) — well, it’s clearly learned some new moves! What should the commanders do? Should they send in the troops already trained for version 1.0? Or train a new battalion?
In reality, they do both: The previously trained troops dive in, but those soldiers’ skills were specific to the other guy’s fighting technique. They’re not as strong a match for this kinda newish enemy. So while the grunts are doing their best to hold the pathogen at bay, the commanders are quickly training a new battalion that can outfight this new guy.
They’ll succeed (the currently authorized vaccines do mostly work against the current variants of concern), but you may develop some symptoms before your immune system fully defeats this variant. A newly formulated vaccine specific to that variant is a training exercise to get that second battalion ready before the body encounters the real variant in the wild.
What experts are saying
From a cursory review of articles on the topic, experts seem mostly split. Several infectious disease experts have told journalists they expect we’ll need boosters, but right now, that’s all speculation. We simply don’t have the data to say one way or another.
Meanwhile, a coalition of 50 public health organizations called the People’s Vaccine Alliance conducted a survey of 77 global infectious disease experts and reported that two out of three of them believe the virus will mutate enough that the current vaccines will be ineffective. I’m extremely skeptical of that finding (though it could be the wording of the survey that’s the problem). It’s taken nearly a year for a few variants to emerge that even partly evade the current vaccines. (The current vaccines are fully protective against the U.K.’s B.1.1.7 and slightly less effective against South Africa’s B.1.351, Brazil’s P.1, and California’s B.1.427/B.1.429.)
Further, all the current variants of concern are converging on the same handful of mutations, suggesting the virus is, so far it seems, running out of tricks. There’s no current indication that we’ll see such radical mutations that the virus can completely evade protection from vaccines, and no expert I’ve spoken to is genuinely expecting that. True, anything is possible, but current data do not support that concern.
That said, the longer it takes to vaccinate everyone, the more time the virus has to mutate. My guess is that the experts most worried about mutations that will escape the vaccine are those from countries with the least access to current vaccines, so their concern is understandable.
What pharmaceutical companies are saying
Pfizer CEO Albert Bourla said in early April that it’s likely people will need a third dose “somewhere between six and 12 months, and then from there, there would be an annual revaccination.” Frankly, unless he knows of data showing declining antibody levels in trial participants that hasn’t been released, there’s no evidence to support either assertion, that we’ll need a third shot within a year, or that we’ll need annual shots.
Johnson & Johnson CEO Alex Gorsky told the Washington Post in early March that the company has begun a trial to test the effectiveness of a second dose, but he didn’t see a reason to think a second dose would be needed until data showed otherwise. However, he told CNBC in early February that annual shots may be necessary. Again, there’s currently no evidence to suggest annual shots will become a reality.
Moderna CEO Stéphane Bancel also recently said booster shots will eventually be necessary, though he added — accurately — that it’s too soon to know when.
All three companies are working on booster shots, and Pfizer and Moderna have begun clinical trials with them. I trust Bancel’s response most here, but I haven’t seen data to persuade me to believe that a booster will definitely be necessary. I’ll wait for the evidence.
I also can’t ignore the fact that all three CEOs have a vested financial interest in producing boosters. Vaccines aren’t usually big moneymakers for manufacturers, but right now, the market is up to 7 billion people. That changes the financial calculations a wee bit, though it’s unclear how much the companies would make from boosters, as this excellent Quartz article explores.
Vaccine formulations addressing the variants are a different issue. All three companies are also working to develop vaccines targeting different variants, and Moderna has already begun a trial for one vaccine specific to B.1.351 and a second that combines their current vaccine with the B.1.351-variant one. Fortunately, the vaccine development method these companies used makes it pretty easy to update their vaccines for new variants. It’s not quite plug-and-play, but it’s as close as you can get. Pfizer and Moderna only need to tweak the mRNA sequence in their vaccines, and then they should work just as well against the variant with those tweaks as their current vaccines work against the previously dominant strain.
What Anthony Fauci is saying
Fauci told MSNBC on April 12 that current evidence shows the mRNA vaccines are fully effective for six months, “but it’s highly likely that it will be effective for a considerably longer period of time.” To find out, we have to follow people to see when protection drops off, such as when more Covid-19 cases occur in vaccinated people. He seemed optimistic but said if it turns out protection drops in a year or a year and a half, “we very well may need booster shots to keep up the level of protection.” Still, he made it clear that it depends on the data.
What kind of data? Fauci told ABC around the same time that it depends on the correlate of protection, which refers to biomarkers indicating how much immune protection we need so we don’t get Covid. Correlates of protection are often discussed in terms of antibody levels, called titers. For some diseases, we know the minimum titers necessary to prevent disease, but we don’t have that information for Covid-19 yet.
Further, antibodies aren’t the only form of “immune memory” the body has. Remember the generals (T cells) and colonels (B cells)? Even if most of the grunts (antibodies) are gone, the T and B cells may have enough memory to train a new batch of soldiers quickly enough to prevent disease. That’s why tracking actual Covid-19 cases will be especially important.
Fauci concluded the ABC interview saying he thinks we’ll know whether boosters will be needed by fall. If we start seeing a slope in antibodies by fall, mathematical models can estimate when they’ll drop so low that they provide too little protection, but again, we won’t know until we get the data.
Another key question is: Are we seeing an increase in Covid-19 cases in vaccinated people yet? The answer: No.
As of April 20, the CDC has received reports of 7,157 breakthrough infections — an infection that “broke through” the defenses the body produced after vaccination. Just under a third of those (31%) had no symptoms, and 46% were in people at least 60 years old. Although 7% of people were hospitalized and 1% (88 people) died, not all the hospitalizations or deaths were due to Covid-19.
Now consider that, as of the same date, 87 million Americans have been fully vaccinated against Covid-19. We can’t directly compare the infections to the number vaccinated because infections are undercounted — not all of them are getting reported. But we can get a sense of just how unlikely it is to get sick after vaccination. If the rate of infections starts climbing substantially, or if we see an increase in infections among trial participants, that will signal that immunity from vaccines might be dropping off.
The bottom line on boosters
We won’t know whether we need booster shots or an additional vaccine dose specific to any variants until we see a decrease in protection from the currently authorized vaccines. The latter—updated vaccines to address the variants—is more probable sooner. We’ll know there’s a decrease in protection if we see a substantial increase in breakthrough cases (Covid infections in fully vaccinated people).
Unless and until we see that or other data showing a drop in vaccine effectiveness, boosters aren’t necessary. Since we have some preliminary data suggesting less protection against variants, updated shots targeting those are more likely. The “when” depends on the spread of the variants and the completion of clinical trials.
