Mix-and-Matching COVID-19 Vaccinations


A panel of doctors explains whether or not someone can get a different COVID-19 booster from their original vaccinations and how they compare.

Peter Salgo, MD: Can you mix and match? In other words, if you get a Pfizer vaccine, can you boost with Moderna? If you get the mRNA, can you boost with one of the recombinant DNA vaccines?

Jason Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS: The answer to that about the mix and matching is finally data based. We have some of that information from a study the NIH [National Institutes of Health] has done. They mixed and matched, and they took the people with the 3 US vaccines and boosted them with different combinations of the other ones. Some with Moderna got Moderna, some got Pfizer, some got J&J [Johnson & Johnson]; we have data on all of those. All of them resulted in immune response. We don’t have clinical data on it as to how many infections were prevented, but the immunologic evidence is there and is sound. The answer to your question is yes.

Angela Rasmussen, PhD: I’ll add that beyond the NIH study there have been studies coming out of Europe, the United Kingdom, and Canada where they have been doing heterologous vaccination just because of supply issues for quite some time. In fact, that’s why I’m also a hybrid. I got Johnson & Johnson in the United States, and then I moved to Canada, and I got a Pfizer shot. Part of that was because I thought I might need one. I wasn’t entirely confident with the J&J data that were continuing to come out. However, part of that was also because I couldn’t figure out how to transfer my vaccination record from the United States to Canada. What made me make the decision was when Canada finally had resolved its supply issues and vaccines were available to everybody, NACI [National Advisory Committee on Immunization], which is Canada’s immunization advisory board, made a recommendation that heterologous vaccination is actually desirable, at least if you start with an adenovirus-vectored vaccine and follow it up with mRNA vaccine. At least people have higher antibody responses.

Now, whether that is going to have a meaningful effect in the real world in terms of increased protection, we don’t know. However, we certainly know that it’s safe. We’ve been doing heterologous vaccinations for a long time for many other vaccine platforms. In general, it’s not something that is a huge mystery. I think it’s only a mystery to people now because they are paying more and more attention to different types of vaccines. Before this pandemic, I certainly wouldn’t think of anybody coming in and saying, “I got whatever the flu vaccine I got is and you got something else. I got recombinant, you got egg based.” I’ve never heard of people doing that. I think that’s just because people probably haven’t put a lot of thought into vaccine brand names.

Peter Salgo, MD: Actually, I would beg to differ. I think it’s because they put way too much thought into vaccine brands.

Donald Alcendor, PhD: I want to answer your first question, that is why they prefer one or other. What I’m hearing, and I’m embedded with vaccine teams to vaccinate folks, what I’m hearing from them is one, they want the Pfizer vaccine because the Pfizer is the one that’s been fully approved. That’s one reason. The other one from Moderna is because if you go to the mix and match results of vaccines, then you see that Moderna had better efficacy when the mixing and matching was done. Some people have read that, and that helps their decision.

Peter Salgo, MD: People are reading, people are listening. I haven’t seen this before. Angela’s right, people would come in and say, “Give me a shot,” in the past. Not anymore. Tell me about the actual amount of vaccine in the booster. Is it the same as with the first 2? Is it different? Is it different across manufacturers?

Jason Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS: The Moderna one is a lower dose. The other 2 are the same is the short answer to that. As Donald pointed out, the response was the greatest in the study with the Moderna vaccine, but the dose was different. It was 100 μg in that mix and match study, and the booster’s being used as 50 μg. However, for the Pfizer and the J&J vaccines, the dose is the exact same. There’s no difference from what people received earlier.

Peter Salgo, MD: I suppose from a logistics perspective it’s easier. One vaccine, 1 dose, you distribute it, you give it 1, 2, or 3. Otherwise, you must keep track of what you’re giving, right?

Jason Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS: Yes, and keeping track of it has become important as the pediatric vaccines have moved forward because there have been a few mix-ups where adult doses have been given and so forth.

Peter Salgo, MD: I will tell you that some people I know, when they get their children vaccinated, refuse to go and get their booster on the same day. They don’t want there to be any question on that table with these syringes about which one is the adult dose and which one is the pediatric dose. I think that’s fair.

Donald Alcendor, PhD: I just want to say something about vaccine formulations here. That is, in the vaccine for the children, there has been a bit of a change in the formulation to include a tris buffer. I got a tremendous amount of media attention to answer this question about why is there a change to include a tris buffer in the children’s vaccine as opposed to leaving it the same formulation. It turns out, I had to explain to people that the tris buffer is there in an amount that wouldn’t affect anybody. They were saying this tris buffer would cause all sorts of problems. However, the tris buffer is there to improve the shelf life of the vaccine. They have misinformation saying that this tris buffer is there to cause all sorts of injury to children who would receive the childhood vaccine.

Peter Salgo, MD: Isn’t that the same argument people made about mercury as a preservative? That led to the individual doses that were preservative free?

Donald Alcendor, PhD: That’s right.

Peter Salgo, MD: It’s the same argument. It’s the same strangeness. But you understand that people are concerned about their children.

Jason Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS: I’m saying that buffer is a plus, too. If you look at where these vaccines are being given, increasing its shelf life is going to be necessary when you move it from large vaccination centers into pediatricians’ offices.

Peter Salgo, MD: That’s a real difference. People are hearing about this; the problem is they may be hearing about it in a way that makes no scientific sense.

Donald Alcendor, PhD: Exactly.

Peter Salgo, MD: I want to thank you at home for watching this Peer Exchange discussion. If you enjoyed the content, subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript edited for clarity.

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