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This episode was filmed on January 26, 2021. For up-to-date information on the COVID-19 pandemic, check out our playlist linked in the description.

In some ways, designing and testing vaccines for COVID-19 was the easy part. Now, we face the monumental task of getting those vaccines out to people. And different nations are tackling that effort in different ways.

And adding to the difficulty is the fact that many of the vaccines we have so far were tested using multiple doses. For instance, the vaccine from BioNTech and Pfizer requires two shots, three weeks apart. The government of the United Kingdom, however, has made the calculation that one dose is better than none, and have devised a plan to stretch limited vaccine supplies to reach as many individuals as possible.

To that end, they plan to delay any second doses of the BioNTech vaccine by up to 12 weeks, not 3. And, in rare cases, they may even mix and match, like giving someone their first dose of the BioNTech vaccine, and the second dose of a totally different one. A few other countries are following suit, or thinking about it.

And the U. S. Centers for Disease Control has updated their guidelines to allow for up to six weeks between shots for the BioNTech/Pfizer vaccine.

They’re also allowing six weeks for another vaccine by the manufacturer Moderna, which would normally be spaced only four weeks apart. So… will this work? The short answer is: this is a gamble.

And one that’s not necessarily backed by the data we have so far. Two doses is not unusual for a vaccine in general. In fact, it’s common to have one dose followed by a second “booster” dose of the same vaccine.

Vaccines teach your body to spot invaders, or parts of invaders, by triggering your immune system, which creates antibodies that bind to foreign material. This process creates a kind of memory in your immune system, one that can fade over time after the first exposure. But by giving our bodies a second exposure to the threat, we essentially convince our immune system to take it seriously.

The repeat dose convinces our bodies to keep that memory around for a long time. Many of our new COVID vaccines work according to this scheme. The BioNTech and Moderna vaccines use two doses.

So does a third vaccine from Oxford and AstraZeneca. This is what early testing found would provide the best immune response. Later clinical trials built up from there, and evidence from those trials is what convinced the various regulatory agencies of the world that these vaccines were safe and effective enough for emergency use.

In those trials, BioNTech’s doses were given three weeks apart. Moderna’s were given four weeks apart. But, like we said, countries are looking at waiting as long as six or even 12 weeks between doses.

And it's hard to predict what effect delaying the second vaccine dose will have. For one thing, protection isn’t linear. You aren’t half-protected after getting half the shots.

We also don’t know yet whether COVID vaccines completely stop infection, or just keep people from getting sick. And BioNTech/Pfizer and Moderna’s clinical trials weren’t designed to test using extended schedules, or using different vaccines as the second booster. That said, we can at least peek under the hood of those trials to look for clues.

Specifically, we need to look at what happened in participants between their first and second doses. When Pfizer did that, they suggested that the first shot was about 50 percent effective at stopping symptomatic cases of COVID-19, though they cautioned against making conclusions based on this. That’s compared to about 95 percent after the second shot.

However, there’s more than one way to look at data. An analysis by the UK’s expert committee on vaccines suggests the first dose may actually be closer to 90 percent effective. That’s because they looked at the period between dose one and dose two, but discarded the first two weeks of data, since it’s thought that the vaccine hasn’t really kicked in yet at that point.

This does line up with what we think’s going on biologically. I mean, it takes time for immunity to ramp up. But doing the math like this is controversial.

And other data, from research done in Israel, now suggests the first dose of the BioNTech vaccine may not be as effective alone. They’re giving numbers around 33 percent, rather than 50 or 90 percent. But their results are also controversial.

The data from the study hasn’t been made publicly available or been peer-reviewed yet, and it was an observational study, not a controlled trial. Meanwhile, Moderna estimated the efficacy of their vaccine after just one dose was about 80 percent. But they also cautioned that this data was based on small, non-random samples and, like Pfizer, said it can’t support a definite conclusion.

Both companies have said that they recommend following the vaccine schedule supported by their respective clinical trials. Now, there is the AstraZeneca vaccine as well. And giving a second shot up to 12 weeks later is within their recommended dosing schedule.

So… one out of three ain’t bad? Complicating things, we also have no idea how long a single dose works for. Like, Pfizer has said there wasn’t evidence to support their vaccine being effective if the second shot is delayed.

Again, the clinical trials just weren’t set up that way. One of the other huge unknowns around the UK and US’s potential plans is that they’re allowing the booster shot to be a different vaccine, in extreme cases, if the original isn’t available. Usually, when you go to the doctor and you get a booster shot, it’s just a second dose of the same thing.

Theoretically, the different vaccines are all training our bodies to produce antibodies to the same virus, so it should work even if you mix and match. Doctors will do this with some established vaccines if they have to, like if there’s a shortage. But the BioNTech and Moderna vaccines use a novel technology and the mix-and-match approach hasn’t been tested, so we don’t know if it will work.

It might be that some subtle difference in the vaccines really does matter. Some experts have even warned that the spaced-out schedule could increase the risk of a vaccine-resistant strain of the virus. Even for AstraZeneca, which did test a longer gap.

This is rare for human diseases, but it’s possible, for the same reasons bacteria can become resistant to antibiotics. If people have enough antibodies to attack the virus, but not enough to completely squash an infection, that might select for mutations that get around the vaccine. And if there are lots of people who aren’t as well-protected thanks to single doses, the odds of this happening increase.

So, overall, it is possible that delaying second doses of COVID vaccines could spread protection to more people and slow the pandemic. But in science, we can’t say we know something if it hasn’t been tested. And there’s one other important piece here.

See, ethics experts have raised serious concerns about both the untested schedule, and mixing manufacturers. That’s because the people who participated in the clinical trials for these vaccines benefited from the strict rules meant to protect them. The experts are saying that suddenly changing how we give out the vaccines is basically conducting an experiment without any of that protection.

And those experts are calling for actual testing before the UK, US, and others go off script. Because the whole point here is to keep people safe. So this is a gamble.

And it could pay off… the question is whether it’s worth the risk. Thanks for watching this episode of SciShow, and thanks to our patrons for helping us make it happen. Y’all are helping us take complicated, scary topics and hopefully make them a little less scary and complicated.

And we could not do that work without you, so thanks. If you’d like to help out, check out patreon.com/scishow. [♪ OUTRO].