Mixing COVID-19 vaccines could be making the best ‘of a bad situation’

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In the midst of a variant-driven third wave, Canada’s beleaguered vaccine advisory panel is considering whether to endorse mixing vaccine doses.

With supplies of AstraZeneca mostly exhausted, and future delivery dates uncertain, the National Advisory Committee on Immunization is weighing up options for swapping second, booster doses.

There is no reason why people who have had one dose of AstraZeneca shouldn’t receive a second dose of the same vaccine, the panel said Monday, despite reiterating its earlier stance that mRNA vaccines — Pfizer-BioNTech and Moderna — are “preferred” over the AstraZeneca and Johnson & Johnson shots, due to a remote risk of an unusual type of blood clotting complication.

But with delays in AstraZeneca supplies, and 36 million doses of Pfizer and Moderna scheduled to be delivered over the next two months, mixing for some people, potentially hundreds of thousands, may become unavoidable.

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The panel’s co-chair has already said that Pfizer and Moderna shots are similar enough that people who receive the Pfizer shot could receive Moderna for their second dose, and vice versa. “Let’s say you run out of Pfizer’s vaccine because you’ve administered all your doses, or you don’t know what your patient had at first … this eases up the complexity,” Dr. Caroline Quach-Thanh told the Canadian Medical Association Journal in December. Quebec has already announced it would substitute the second Moderna dose with a Pfizer dose, if necessary, to fully vaccinate long-term care residents as soon as possible.

But the vaccine advisory group is also considering combining Pfizer or Moderna with AstraZeneca. The panel said it will make recommendations about “next schedules” once it receives more data.

All three vaccines require two doses. Johnson & Johnson is a one-shot jab.

Pfizer and Moderna, both mRNA-based vaccines, deliver genetic instructions that tell the body’s cells to start producing and pushing out harmless pieces of the spike protein found on the surface of the virus that causes COVID-19. The cells make the protein piece, triggering an immune response and priming the immune system to attack the virus should the person later becomes infected with the virus. Tiny droplets of fat called lipid nanoparticles deliver the mRNA into human cells.

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AstraZeneca and the J & J vaccine use a different approach. The AstraZeneca shot, developed with the University of Oxford, uses a weakened version of a common cold virus to introduce coronavirus proteins into cells, triggering the body to generate an immune response.

The safety and efficacy of swapping out vaccines is still unproven, though it is being studied. “In an ideal world, we obviously would have kept to the original study protocols,” Montreal cardiologist Dr. Christopher Labos wrote in the Montreal Gazette. But, like the recommendation by NACI to stretch the gap between “priming” and booster doses out by up to four months, instead of the officially authorized three or four weeks, in order to get at least one dose into more people faster, “the practical realities of the pandemic have forced us to change course and alter our position in an effort to make the best of a bad situation,” Labos said.

The first-dose-fast strategy was bold, “and the right thing to do,” said internal medicine physician and University of Toronto assistant professor Dr. Fahad Razak. “It’s clearly been effective in the United Kingdom.” In January, COVID-19 rates in the U.K. were three times higher than Canada’s. “With smart public health measures” and a delayed second dose vaccine rollout, “their rate is now one-sixth our current rate.”

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“But what’s happening now is that many people (in Canada) will be starting to get close to the timing of that second dose. And they’re going to start to wonder in their mind what they should do,” said Razak, a member of Ontario’s COVID-19 science advisory table.

Meanwhile, the AstraZeneca supply will likely decrease in coming weeks because shots are being held back increasingly in India, which is battling a COVID catastrophe.

“You may have a situation in Canada where people are not able to get a second dose of AstraZeneca,” Razak said.

A combination of vaccines might provoke a stronger immune response. The University of Oxford is leading a major trial exploring alternating vaccines between dose one and two. Hundreds of volunteers aged 50 and older have received alternating doses of the Oxford-AstraZeneca and Pfizer vaccines. The study was recently expanded to include the Moderna and Novavax vaccines.

“What I’m hoping is that we won’t rule out any combinations,” the study’s chief investigator, Dr. Matthew Snape, an associate professor in pediatrics and vaccinology at Oxford, told a press briefing. “That’s how we need to look at it — are there any combinations we shouldn’t be giving because they don’t generate a good immune response, and I’m hoping that won’t be the case.”

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In a preprint posted in March, researchers reported that combining an RNA coronavirus vaccine with the AstraZeneca shot induced a more robust immune response in mice than either vaccine alone.

The Oxford researchers have submitted the preliminary “reactogenicity” data — side effects or adverse reactions —  to the Lancet “and this will hopefully be published in the next week or two,” Dr. Maheshi Ramasamy, an investigator with the Oxford Vaccine Group said in an email. The immunogenicity data — how well the combinations work in rousing an immune response  — will not be available for another month.

Unlike early vaccine trials, the study is being done in the time of variants.

Are there any combinations we shouldn’t be giving because they don’t generate a good immune response

Some variants, like the one that emerged in South Africa, appear less responsive to some vaccines. “If you use two different vaccines that trigger your immune response in two different ways, maybe you overcome some of that vaccine escape that you’re seeing from these variants,” Razak said.

Still, the human immune response is complex, he said. And, 16 months out, the virus keeps surprising us. While alternating vaccines seems a reasonable approach to consider, the U.S. Food and Drug Administration cautioned in January that, until there are data supporting doing so, “we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19.”

The AstraZeneca vaccine carries an estimated one in 100,000 risk of a clotting complication known as VITT, or vaccine-induced thrombotic thrombocytopenia, after the first dose. However, there appears no heightened risk after the second, Razak said, though it is being studied intensely. “If there was a strong signal that after that second dose you see an increased risk, people would pick that up now. Because they are looking so closely,” he said.

• Email: skirkey@postmedia.com | Twitter: sharon_kirkey