Studying if two vaccines are better than one
Researchers examine added power of receiving two different vaccines
With one shot to spark an immune response and a second to boost it, most of the leading COVID-19 vaccines require two doses — but would mass vaccination be less daunting if we could mix and match?
That’s the question being asked by researchers from the University of Oxford, who have begun enrolling volunteers for a new study that will look at whether, instead of getting two identical shots, you can instead receive two different vaccines and still be well protected from COVID-19.
It’s an as-yet untested strategy that offers the hope of easing pressure on vaccine supply lines, currently stretched to the brink by production snags in Europe.
But more than that, some experts say that with questions swirling about how long immunity lasts and what new variants could mean for vaccine effectiveness, getting a dose of two different vaccines might be a way of hedging your bets and ending up with broader, stronger protection against disease.
Mixing vaccines is not something experts would normally recommend, says Julie Bettinger, an associate professor of pediatrics at the Vaccine Evaluation Centre at the University of British Columbia. But with a pandemic raging, these are not normal times.
“If you’re able to mix them, then that just expands your options in terms of reaching more people with a vaccine,” she says. “That might be a real way to get the pandemic under control right now.”
Of course, researchers first have to figure out whether this approach actually works and whether it’s safe.
According to a release posted to the Oxford University website last week, researchers there plan to recruit 800 volunteers over the age of 50. Some will get the normal two shots of the Pfizer vaccine or the Oxford AstraZeneca version, but others will get one of each, spaced out by either four or 12 weeks.
At the end, researchers will compare the volunteer’s immune responses by measuring the byproducts left behind, called antibodies and immune cells called T cells.
“If we do show that these vaccines can be used interchangeably in the same schedule this will greatly increase the flexibility of vaccine delivery, and could provide clues as to how to increase the breadth of protection against new virus strains,” chief investigator and associate professor Matthew Snape said in the release.
Supply issues aside, to Alan Bernstein, a member of Canada’s vaccine task force, it’s the potential of broader protection that is most promising about this research.
“The motivation should be about, “Is this giving us a better immune response?’ ” said Bernstein, who is also the president and CEO of CIFAR, the Canadian Institute for Advanced Research.
“And this won’t be answered in this trial, but is this a way of getting around, potentially or possibly, the variants that are coming up?”
Using two vaccines together isn’t totally uncharted territory: It’s been used against other diseases and Sputnik V, the Russian COVID-19 vaccine, uses a slightly tweaked version for the second dose.
But for most of the major COVID-19 vaccines rolling out, it just hasn’t been tested.
To understand the potential of this mismatched vaccine plan to offer more protection — the technical term for it is a “heterologous prime-boost” — requires an appreciation of the complexity of the human immune system.
When it comes to fighting off disease, your body has multiple tools in its tool kit and not all of the current vaccine contenders are swinging the same one. To use another metaphor, some vaccines are teaching your immune system judo, while others are coaching it to box but, as the virus continues to spread, at some point it might be nice to know both.
The first two vaccines to get authorization in Canada have been the doses made by PfizerBioNTech and Moderna. Part of the reason they were first across the finish line is because they’re using the same “platform” or general approach; one that involves mRNA, which is relatively quick to make once you know how.
Messenger RNA is basically a tiny set of instructions by which researchers can tell your cells to make a certain protein — in this case, the vaccine is telling your cells to make little coronavirus spike proteins, which in turn teach your body how to fight off a larger infection.
What this technique is particularly good at, according to Bernstein, is prompting your body to make neutralizing antibodies, which work by latching onto bits of virus and stopping them from infecting you.
But some of the newer crop of vaccines on deck, including the one made by Oxford University and AstraZeneca and the one made by Janssen, both currently under review by Health Canada, do things a little differently.
Known as viral vector vaccines, they use a different virus — in the above two cases, one normally found in chimps — to sneak a bit of coronavirus DNA into your body and get it to make a spike protein.
So far, AstraZeneca’s vaccine has been good at getting neutralizing antibodies in play, but not as good as the mRNA vaccines, Bernstein says.
Instead, its special skill seems to be stimulating a type of T cell that recognizes cells that have been infected by the virus and kills them. They also seem to recognize more of the virus than just the spike protein. So that’s a different type of protection altogether.
The potential of mixing vaccines — and again, this would have to be supported by studies — is that you might end up with both defences at your disposal.
“When you’re fighting a world war, you need a strong air force, a strong navy, and you need strong land troops. Our immune system is like that,” as Bernstein puts it.
Bernstein said Canada should consider doing this kind of research here. It would be easier to recruit volunteers, he said, because the virus is spreading more slowly here, so there are more people that have never been exposed, and because currently we also have fewer vaccines.
But he adds that doing trials in Canada would be useful as the virus progresses.
“There may be different variants in Canada, given the slightly different population structure of people in Canada, so we might get different results,” he said.
“I think Canada should be contributing to these global trials.”