U.S. health officials want you to get another shot of Covid-19 vaccine. But some experts in the vaccine world don’t think we should be using the “B” word to describe that extra jab.
Don’t call it a booster, they insist.
Instead they argue an additional dose of one of the messenger RNA vaccines should be termed a third dose, a part of the primary series of shots that awaken and arm immune systems to deal with the threat of the SARS-CoV-2 virus.
Is it semantics? Does it make any material or practical difference what we call it? Does approving use of a booster shot put the country on a slippery slope toward annual Covid vaccinations? STAT asked a number of experts for their views. Let’s explore what we learned in the process.
Stanley Plotkin says: Don’t call it a booster.
Earlier this week, Stanley Plotkin called in to a meeting of the Advisory Committee on Immunization Practices, which guides the Centers for Disease Control and Prevention’s vaccine policy.
Plotkin needed no introduction to anyone who works in the fields of immunology or vaccinology. He developed the rubella vaccine — now bundled in a measles, mumps, and rubella (and sometimes varicella, a.k.a. chickenpox) vaccine — that has been used for decades. He is the éminence grise of vaccine science, and the senior author of the definitive textbook on these preventatives, Plotkin’s Vaccines.
All that to say when Stanley Plotkin speaks, people listen.
During the meeting, Plotkin urged the ACIP to stop talking about Covid vaccine boosters. The third shot should be considered the final dose of the original series of vaccines, he argued. We may or may not need later boosters at a later date, Plotkin said. But for now, the third dose is finishing the job of generating a robust and lasting immune response.
It’s well known in vaccinology that when using inactivated or non-replicating vaccines — vaccines that don’t use a live-virus to trigger an immune response — multiple doses are needed. A priming dose (or doses) is followed four to six months later with an additional jab that helps the immune response to mature, he said. Many vaccines given in childhood are administered in a three-dose series, with a gap of several months between the second and third shots.
Does that mean the original two doses of the Pfizer and Moderna vaccines — given three and four weeks apart, respectively — were poorly timed? Plotkin, who consults with multiple vaccine manufacturers, was not ready to go there. The durability of the immune response would likely have been better had the doses been spaced out further, but going months between dose 1 and dose 2 might have led to more Covid deaths, he told STAT.
He suggested the word booster carries a connotation that is not helpful as the country struggles to increase Covid vaccine acceptance: “My point, basically, was that calling them boosters implies that the first doses were failures.”
“Calling the third dose a booster is immunologically incorrect and also gives the wrong impression that somehow the vaccines failed when they could not really have been expected to give a long-lasting immunity from the first doses,” Plotkin said.
Yes, but Pfizer is calling its third dose a booster…
The Pfizer-BioNTech partnership has strung together a series of firsts with Covid vaccines. It was the first vaccine to be put into use, the first to get full Food and Drug Administration approval, and is the first to apply to give a third dose — which the company is calling a booster.
Pfizer is not asking the FDA to revise the license for Comirnaty, its Covid vaccine, to classify it as a three-dose vaccine.
“We expect the primary series to remain at two doses for healthy individuals,” the company said in an emailed reply to questions from STAT. “Our application to the FDA requests approval of a booster dose for those 16 years of age and older.”
[It’s important to understand that this application relates to a third dose for everyone who got two doses of the Pfizer vaccine. Earlier the CDC’s vaccine advisory panel, ACIP, recommended that people who are moderately to severely immunocompromised be given this vaccine in a three-dose series, because they do not respond adequately to two doses.]
Forget about what it’s called — is it needed?
Increasing reports of breakthrough infections in fully vaccinated people fueled the decision to use third doses of the mRNA vaccines. The Biden administration points to more infections among people who were vaccinated early in the vaccine rollout to suggest protection is waning. Scientists who are critical of the decision argue that the rise in breakthrough cases coincided with the surge of the more infectious Delta variant and declining support for social distancing measures, making it difficult to tease out what is really going on.
Kathleen Neuzil, director of the Center for Vaccine Development at the University of Maryland Medical School, thinks getting more adults vaccinated, both domestically and internationally, and getting children younger than 12 vaccinated would do more to control Covid than giving healthy Americans a third dose at this stage.
“I am clearly in the get-vaccine-to-the-world camp,” Neuzil said. “It is absolutely the right thing to do, it’s also the smart thing to do. … We are going to be chasing variants forever if we can’t get the majority of the population vaccinated and convert this from a severe disease to hopefully just a nuisance disease.”
Ali Ellebedy, who studies the immune system’s response to infection and vaccination, isn’t sure healthy adults currently need a third jab of the Pfizer or Moderna vaccines, based on what he is seeing.
His laboratory at Washington University in St. Louis, studies the lymph node and bone marrow of vaccinated people to see how their immune systems are engaging to generate protection against SARS-2. Most of the people his group has studied are still generating a response to their second dose of vaccine — even six months after that dose was received, he said.
“I don’t think that will be hurt by additional immunization. I just think that well, we really didn’t even reach the full potential of the second dose [yet],” said Ellebedy, who is an associate professor of pathology and immunology.
“Usually, you give an additional immunization to re-engage the system. But … at least in most of the individuals we looked at, the system is already engaged,” he said.
Ellebedy thinks a third dose will help the people who get it, though he’s not sure whether a third-shot program will have a clinically important impact. By that he means it may not change the risk of severe disease that twice-vaccinated people face — because they already have good protection. “The immune memory we are seeing is really robust,” he said.
We probably wouldn’t be talking about third shots or boosters — whatever you want to call them — but for the emergence of the Delta variant, he said. “Delta really changed the game.”
For the record, Ellebedy will get a third shot when he’s eligible. “I do think there will be a benefit from having a third shot.”
The jury’s still out on fourth shots, fifth shots, etc.
Pfizer CEO Albert Bourla has publicly raised the prospect that annual Covid shots may be required. The company’s official line is that annual jabs may be needed, but there aren’t enough data yet to say one way or the other.
Plotkin agrees. “The idea of an annual booster will depend on what happens to the antibody level after this third dose,” he said. “I would hope that the antibodies would persist pretty well. But if I’m wrong and also if the virus changes considerably — that like with influenza, you need to adjust the vaccine to the mutations of the virus — then I guess I could imagine annual vaccination. But we just don’t have the data yet.”
Ellebedy said, having seen the immune response’s reaction to vaccination, he doubts we’ll need fourth shots in the near future. But he added the caveat that until the Delta variant emerged, he didn’t think we’d need a third dose so soon either.
To-may-to? To-mah-to? Does it matter what we call dose 3?
Maybe not, said Jeffrey Duchin, health officer for the Seattle and King County public health department.
“I don’t think it’s that meaningful for the general public,” said Duchin, who is also a professor of infectious diseases professor at the University of Washington.
“What the general public wants to know and it needs to know is how many doses do I need? And when do I need to get them? And the scientists need to figure out whether those doses are going to be in the form of a primary series that would be relatively closely spaced together over a period of months or primary series and then a booster, which typically comes at a more delayed timeframe, down the road maybe years,” he said.
It’s also important for people to understand that the scientific and public health communities are still learning about the best way to use these vaccines, Duchin said. That means as new knowledge is acquired, recommendations on use of the vaccines — including, potentially, boosters — are going to evolve.
“I do think that this is going to be an evolution in our understanding and fine tuning of how we use these vaccines based on what we learn. So, the next set of recommendations may not be the last,” he said. “They’ll be the best set of recommendations that we can make based on the information that’s currently available. And I think as we learn more, we may find that we can make improvements. Maybe, maybe not. But I think time will tell what’s the best way to use these vaccines.”
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