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As the Covid-19 vaccine rollout began to gain momentum in early 2021, so too did a handful of variants of the SARS-CoV-2 virus, including those originating in the United Kingdom, South Africa, and Brazil. In addition to the sense of relief that came when the highly anticipated shots finally started making it into arms, it became increasingly difficult to ignore the looming threat of these emerging strains — including the fact that they weren’t widely circulating when the vaccines were developed. 

Viruses evolve constantly, but rarely in front of a captive and traumatized worldwide audience. Immediately, there were questions: Would the exceptionally high efficacy rates demonstrated during the clinical trials decrease dramatically once the new variants were factored in? Will the vaccines we are getting offer enough (or any) protection against these strains? If not, will we need a booster?

Fortunately, early data suggested that the Covid vaccines were effective against the first few widespread variants. But with each new dominant strain have come renewed fears that the vaccines we were counting on to end the pandemic may not be up to the job. This has happened most recently with the Delta variant, which is more highly contagious than the original version of the virus — thanks, in part, to how quickly it grows inside a person’s respiratory tract — and is now the dominant coronavirus strain in the United States. 

As our knowledge of the Delta variant increased, so did the number of questions about Covid vaccine boosters. The combination of curiosity, concern, and confusion over boosters reached fever pitch when, on July 8th, pharmaceutical company Pfizer announced plans to seek emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) for a Covid-19 vaccine booster shot in August 2021. A few hours later, the Centers for Disease Control and Prevention (CDC) and FDA released a joint statement saying that fully vaccinated individuals don’t need a booster at this time — resulting in more confusion and questions.

While we’re far from having all the answers, having a better grasp on variants, boosters, and other variables can help us make sense of the latest headlines. Here’s what we know so far.

What do we know about the new Covid-19 variants?

After living through a global pandemic, the last thing you want to hear is that the virus behind it all has been evolving, and is now spreading in multiple iterations. But not only is it important to keep in mind that it’s incredibly common for viruses to mutate over time, but also that all variants aren’t equally dangerous. The threat of a particular strain comes down to a number of factors, including how similarly it acts to the original virus, and how quickly the evolution is taking place. 

Take HIV, for example. It mutates at a much faster rate than other viruses, which is making it incredibly difficult for scientists to create a vaccine that would be able to trigger the necessary immune response while keeping up with its evolution. How fast are we talking? As Dr. Larry Corey, a virologist at Fred Hutchinson Cancer Research Center and co-founder of the HIV Vaccine Trials Network (HVTN) told Rolling Stone in April, when it comes to mutations, “what Covid does in two months, HIV does in one day.” This is one of the reasons why it was possible to create multiple Covid-19 vaccines in less than a year, but an HIV vaccine does not yet exist after decades of research. Both viruses evolve, but at very different rates.

In fact, as far as variants go, Dr. Kirsten Lyke, professor of medicine at the University of Maryland School of Medicine and researcher at their Center for Vaccine Development and Global Health, says that “we’ve been lucky” with the ones that have emerged and spread so far. That’s because while the new strains may be more transmissible than the original SARS-CoV-2 virus, there are still enough similarities that if someone had an adequate immune response to the Covid-19 vaccine, it appears that they are also protected against the recent variants of concerns, like Alpha, Beta, and Delta.

Of course, that’s not to say that the current iterations of the Covid-19 vaccines will work against all of the future variants — which is one of the reasons we’re talking about booster shots.

Why would a Covid-19 booster shot be required?

Before getting too deep into boosters, let’s look at why we might need one in the first place. As the name suggests, booster shots are follow-up doses of a vaccine, given to bolster the immune system if the initial vaccination is no longer effective. That’s right: although much of the conversation surrounding Covid vaccine booster shots makes it seem as though they’re inevitable, it’s still unclear whether we’ll need one at all. And based on the limited data that is currently available (more on that in a minute), at this point, there is no definitive evidence that a Covid booster is necessary.

So how would we know if that changes? According to Lyke — who is currently co-principal investigator of a National Institutes of Health (NIH) multicenter clinical trial looking into mixing different combinations of Covid-19 vaccines and boosters — based on where we are right now in the pandemic, there are three scenarios that would require a booster shot. 

The first, she explains, would be if we get to a point where the emerging variants “are sufficiently able to escape the vaccine” and our initial vaccinations no longer offer sufficient protection. Another possibility is that the current vaccines’ ability to trigger an immune response to the novel coronavirus wanes over time — something Lyke says isn’t uncommon. Finally, a booster may be necessary for people who didn’t mount enough of an immune response after receiving their initial Covid-19 vaccination because of a compromised immune system or recent transplant. 

Along the same lines, booster shots can take one of two formats: They can either be an additional dose of the original vaccine (to give the recipient’s immune system the opportunity to produce more antibodies), or an updated formulation designed to extend the vaccine’s protection to additional variants. Currently, Pfizer and Moderna each have clinical trials underway to evaluate both third doses of their initial vaccine, as well as new booster vaccines targeting the emerging strains. While Johnson & Johnson has not yet announced their own Covid vaccine booster studies, Lykes’ NIH-sponsored clinical trial includes people who received the J&J shot initially, and aims to identify the most effective booster option for them.

How are the current Covid vaccines holding up?

Though it’s still too soon to know whether we’ll end up needing a Covid-19 vaccine booster (and if so, what kind), data demonstrating how the current vaccines protect against the new variants have started trickling in. At this point, Pfizer, Moderna, and Johnson & Johnson have each released findings from internal lab studies indicating that their respective vaccines provided sufficient protection against a number of variants, including Delta. 

Some of the first real-world data came out of Israel on July 5th, when the country’s Ministry of Health announced the results of their own epidemiological analysis that found that the Pfizer vaccine is roughly 64 percent effective against preventing infection and symptomatic illness caused by the current SARS-CoV-2 variants. While that may sound like a substantial drop compared to the 95 percent efficacy rates reported after the vaccine’s initial clinical trials, the Israeli study found that the Pfizer vaccine was still around 93 percent effective in preventing cases involving serious illness and hospitalization.

There is also new insight into why the Pfizer and Moderna mRNA vaccines are able to offer protection against several variants, thanks to a study published in the journal Nature on June 28th. The findings of the research suggest that the Pfizer and Moderna vaccines may trigger an ongoing immune response to the SARS-CoV-2 virus that could offer lasting protection — including against some emerging variants.

Antibodies — and, to a lesser extent, T-cells — have gotten most of the attention when it comes to Covid and immunity, but that narrow focus overlooks the lesser-known-but-mighty B-cells, which are responsible for producing the antibodies. “After vaccination, our immune system sets up ‘training camps’ to perfect the immune cells responding to the vaccine,” says Dr. Ali Ellebedy, an immunologist at Washington University in St. Louis, and lead researcher on the study. “These camps are called ‘germinal center reactions,’ and they train vaccine-responding B cells.” 

According to Ellebedy, when a vaccine effectively prompts a person’s body to establish these B-cell training camps, there are two main outcomes: Optimized antibodies that strongly bind to the vaccine (in this case, the SARS-CoV-2 spike protein), and cells that have been granted immortality by being transformed into immune memory cells. 

“We were not surprised to see a robust germinal center reaction after Pfizer’s SARS-CoV-2 vaccine, given all the data that came out showing how strong the responses in blood are,” Ellebedy says. “What we found remarkable is that these germinal center reactions persisted for months after vaccination, indicating that a lot of perfected immune memory cells have been ‘graduating.’” In other words, like the virus, our own B cells continuously evolve in order to tailor the antibodies they produce so that they have the potential not only to recognize the original strain, but the emerging variants as well. 

But despite the vaccines’ durable immune response, booster shots aren’t off the table. “Our findings tell us that if the virus had not evolved, we would not have been discussing the need for boosters — at least for healthy people,” Ellebedy explains. “But now that multiple variants of concerns have emerged, the situation with the variant has become the main determinant of whether we will need a booster or not.”

Why was there confusion over Pfizer’s announcement?

This brings us back to Pfizer’s recent announcement about the “encouraging data” seen in an ongoing booster clinical trial involving a third shot of their current Covid-19 vaccine, and their plans to share their findings with the FDA as soon as next month, and apply for emergency use authorization soon after. Immediately, some scientists were critical of the pharmaceutical company’s move, noting that it was still unclear when or even if a booster will ever be required, and suggesting that Pfizer’s push for boosters was a way to guarantee continued demand for their vaccines.

“Pfizer and BioNTech, of course, are industry, and they’re interested in advancing their products,” says Dr. Wilbur Chen, the chief of the adult clinical studies section within the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine. “They certainly are aware that the booster dose variant discussion is important, are super excited that they’ve got this positive data, and are broadcasting that they’re going to publish it soon.”

And while there’s nothing out-of-line about Pfizer’s research process and plans for the future, their announcement itself has been the source of some confusion. “The lay person hears about all these different developments and thinks that when a company is going forward with an FDA application, that it’s almost like a shoo-in for [the vaccine] being used immediately,” Chen tells Rolling Stone. “After seeing how quickly Covid vaccine research and approval moved [in the second half of 2020], resulting in shots in arms, people are now accustomed to that process and timeline. But that’s not the way that we’re going to do it with boosters, because yes, we’re going to have a booster dose ready on the shelf and authorized potentially, but we’re not going to implement it until the data shows that we need to use it.” 

That’s why the CDC and FDA stepped in to clear things up a few hours after Pfizer’s news release. “In their joint statement, the CDC and the FDA are saying, ‘OK, you’re hearing about positive data, and that it’s going to be submitted to regulatory authorities, but that does not mean that the government is deciding to implement booster doses now,’” Chen explains. But the agencies also stipulate that they’re continuing to review new data as it comes in, and “are prepared for booster doses if and when the science demonstrates that they are needed.”

What’s next for vaccine booster research?

While the data currently available suggest that boosters are not needed at this time, we still have no idea what’s next for the vaccines and the variants. “COVID has been such a learning curve,” Lyke tells Rolling Stone. “It’s almost impossible to make a prediction, and anyone that says that we absolutely will need boosters, just doesn’t know.”

For this reason, Lyke says that it’s important to conduct research on boosters now so that if the day comes when Covid vaccine boosters are needed, we’ll have the necessary evidence at hand. “It remains to be seen if a new variant comes down the pike that completely manages to evade the [current] vaccines’ coverage,” she notes. “That would be kind of a nightmare scenario, and we would have to really scramble, because everyone would have to be boosted.”

The good news is that if or when we get to the point of having variants that require a more targeted booster, researchers won’t be starting from scratch. “That’s why as scientists, we like the mRNA approach,” Chen explains, “because as long as you have the sequence of the new variant virus, you can pop that in and make a new booster dose that reflects that variant pretty quickly.” 

But even if the process of creating a booster vaccine formulation is relatively straightforward, there is still a need for additional research before one is administered. For example, the NIH-funded clinical trial Lyke is overseeing aims to answer two key questions about potential boosters: Are they safe? And what kind of immune response will these boosters generate?

“Essentially, we have questions on the need for boosters in the future, and the time to answer those is now, in the summer, when the COVID prevalence is pretty low, and people are pretty well-vaccinated,” Lyke explains. “That way we’ll have all the data in hand, and can make the tough decision moving forward, because if we’re going to do another mass vaccination with boosters and everyone gets one injection of something, we really want to know what the best ‘something’ is.” 

Why scientists are focusing on continued vaccination, in addition to studying the new variants. 

The steady stream of news alerting us to emerging SARS-CoV-2 variants — each seemingly more dangerous than the last — has left us in a perpetual cycle of pandemic panic, but Dr. Sarah Fortune, chair of the department of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, says that this shouldn’t cause us to lose focus on the continued rollout of the initial Covid vaccines.

“From the perspective of pathogen evolution, I think that the questions focusing on one variant — Delta, Lambda, probably with Gamma, Theta, [and] Zeta to come — are missing the point,” Fortune tells Rolling Stone. “There is still a huge amount of virus in the world, and a huge number of non-immune people who can be easily infected.” And unlike the approximately 24 percent of American adults who plan to opt out of getting the Covid vaccine, people in other parts of the world who haven’t yet been vaccinated aren’t necessarily in that category by choice. According to data from the University of Oxford, only one percent of those living in low-income countries have received at least one dose.

In addition to the human toll, the continued spread of Covid-19 is a threat to global health because as long as it circulates, the virus has the opportunity to further evolve — spinning off more transmissible variants. “There is not evolutionary pressure for the virus to cause severe disease per se, and so some of the variants might be more ‘dangerous’ and some might be less ‘dangerous,’” Fortune explains. “But as a general principle, evolution favors transmission.”

And while it’s too early to tell how the evolution of the SARS-CoV-2 virus is going to play out — and consequently, what that means in terms of a potential booster shot — Fortune stresses the importance of expanding the worldwide vaccine rollout. “Right now,” she says, “the single most important thing that we can do is continue to rapidly push vaccine coverage to try to get the global reservoir of virus down — so basically, the virus has fewer shots on goal.”

Lyke agrees. “If there are people out there that haven’t been vaccinated,” she says, “our first message is for goodness sake, go and get vaccinated — whatever you can get access to — because they all still have very good efficacy against severe Covid and hospitalization.”