Get Ready for the Covid-19 Vaccine Mix-and-Match Dilemma

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Journalism at Bloomberg News is a collaborative, cross-disciplinary, multi-time-zone endeavor where stories often begin with simple queries. An impromptu chat between a few reporters and editors recently imagined a hopefully not-so-distant future with multiple, safe, functional coronavirus vaccines—and some potential dilemmas. Please note that this is not medical advice. The Editors

● PETER COY
New York ▷ Bloomberg Businessweek economics editor

Have we written anything on the possibility of a vaccine cocktail—i.e., could people get more protection by taking multiple vaccines? I guess this would depend on whether the vaccines respond to different targets or have different mechanisms of action.

You can see why it would be hard to test the safety and efficacy of a vaccine cocktail. Pharma companies don’t have an incentive to cooperate by testing their vaccines jointly.

● JASON GALE
Melbourne ▷ Senior editor, Asia editing hub

It’s going to be virtually impossible to test the safety and efficacy of vaccine cocktails in animals, let alone people. My understanding is that labs doing animal studies are overloaded already, and who’s going to fund the research? Without proof-of-principle animal studies, it’s hard to see cocktails being tested in people.

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But it sort of makes sense. The vaccines in development use different approaches and often different bits of the spike protein. We know already that an initial priming shot seems to elicit a better response.

● MICHELLE CORTEZ
Maple Grove, Minn. ▷ Health-care Americas senior reporter

There would be some scientific challenges since they would all be going after the same target. There are vaccine combinations, but the components neutralize different viruses (i.e., MMR for measles, mumps, rubella). I haven’t heard of vaccine cocktails in the same way that we have drug cocktails, each hitting a different component of the same target. You would want to make sure they don’t cancel each other out or—God forbid—overactivate the immune system.

● ROBERT LANGRETH
New York ▷ Health-care Americas reporter

What you are really asking about is an off-label mix and match of Vaccine A and Vaccine B—perhaps because the first one is all that’s available, even though it’s not that effective, and then another one comes along a few months later that’s better. That actually came up on CNN recently, and Francis Collins, the director of the National Institutes of Health, said that’s basically what happened with the shingles vaccine. There was one vaccine, then years later a better one came along, and everyone took both. I imagine there would be a shortage with the coronavirus, however, so you might get turned down if you already got one or might get put on a waiting list.

● MICHELLE CORTEZ
That’s good to know. I’d been thinking you only got one chance, and do you just wait for the best? Also, that multiplies the size of the market.

● RILEY GRIFFIN
New York ▷ Health-care Americas reporter

How do you think pharma companies would articulate all that to the general public, Michelle? I’m imagining a scenario where, say, Pfizer and BioNTech bring a shot to market. A patient lines up to get it, even though it’s only mildly efficacious. A few months later, another company, say Merck or Sanofi, brings forth a better option. Perhaps it’s more effective, or maybe it’s just more easily administered, like this “swish-and-swallow” oral vaccine Merck is working on. What’s going to stop this patient from getting that one, too? How will governments keep track of all this? There’s a lot of talk of Phase IV studies on Operation Warp Speed calls, where they’ll monitor safety after shots are administered. But how do you know the average person, eager for protection, hasn’t sought out another?

● MICHELLE CORTEZ

If the vaccines were administered only by your doctor, there might be some control, but since you’ll practically be able to get it while you’re at, say, the gas station, it’s every person for themselves. What a weird world: Some people may get no vaccine, others potentially too much.

● RILEY GRIFFIN

Remember our colleague Max Abelson’s story a few months back, “Rich and Powerful Jump to the Front of Line for Tests”? I don’t doubt we’re soon going to be writing that same story only about vaccines instead of tests. And this is going to become even more complicated when we have multiple shots, some more effective than others.

● STEPHANIE BAKER
London ▷ European investigations reporter

Robin Shattock at Imperial College London told me back in March he thought his mRNA vaccine may work as a booster to the University of Oxford vaccine to provide longer-lasting immunity, though I never heard Oxford mention that. I worry about unexpected side effects of mixing vaccines if taken within a short time period.

● ROBERT LANGRETH

Mixing and matching two different vaccines, each with two doses, strikes me as crazy. But you can imagine some alternative-medicine doctor trying it. By the way, would insurance companies even cover multiple vaccinations?

● MICHELLE CORTEZ

Shouldn’t be too expensive.

● ROBERT LANGRETH

But the insurance company could still say no and make you pay on your own. Or maybe, during a shortage like the one we anticipate, they’ll implement a policy of one Covid-19 vaccine per person per year, like when they don’t allow you to refill overlapping medicines more than once a month.

● JAMES PATON
London ▷ Health-care Europe reporter

One vaccine expert I spoke with worried that the arrival of the first vaccine, if it proved not very effective, would disrupt trial enrollment for the next vaccine, which might provide better protection, because people would go for the new product and thus be ineligible for tests.

● ROBERT LANGRETH

That’s actually a very big problem if they rush approval of a marginal but technically better-than-nothing shot. Doing so would make it much harder to test other vaccines that may be better and present a difficult problem.

● JAMES PATON

I’ve been talking to a couple of people about that, and I’m sure the companies just getting started with human tests are thinking about it.

● RILEY GRIFFIN

Merck’s and Sanofi’s R&D teams are adamant it won’t affect them and that this world has enough people to test. I was pretty surprised when Sanofi’s head vaccine guy, John Shiver, told me so bluntly: “That’s all feasible if the pandemic continues in the way that it’s been proceeding so far this year. I expect cases are going to accumulate later this year when our Phase III trial starts.”

● JASON GALE

I spoke with an immunologist who says the hope is that once all the vaccines are on the market, this kind of mix-and-match research can be done as a Phase IV study—which he says isn’t that difficult to do and could even be government-funded.

● MICHELLE CORTEZ

I connected with Wafaa El-Sadr, professor of epidemiology at Columbia University and director of the Global Health Initiative at the Mailman School of Public Health. “You don’t mix and match vaccines,” she says. You need to get the immunization the way it was developed; if a vaccine requires two rounds, skipping the second means you may not reap the full benefit. She also says that having so many vaccines in a horse race is highly unusual and that safety issues may arise if people combine treatments: “Without studies of the novel combinations, there is no information on whether it will trigger side effects or decrease the effectiveness.” In other words, as with all medication, take only as prescribed.

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