The powerful case for mix and matching Covid vaccines – people who need it most have been messed around enough

Offer the over-60s who were given AstraZeneca a different vaccine for their second shot
Tourists pass through Barcelona airport last week as holiday season kicks in. Spain is one of the many countries now mixing vaccines.

Tourists pass through Barcelona airport last week as holiday season kicks in. Spain is one of the many countries now mixing vaccines.

Luke O'Neill

Many of the over-60s are rightly aggrieved. They were told the only vaccine available to them was the AstraZeneca vaccine. This is because they were deemed to be at a lower risk of it causing the very rare type of blood clotting called Vaccine-Induced Thrombotic Thrombocytopenia (VITT) which was occurring in younger people. The basis for this decision must therefore have been that if we want to use up the AstraZeneca vaccines in order to reach the important medical  and political goal of getting as many adults vaccinated as soon as possible, it would be safest to use the AstraZeneca vaccine in people aged between 60 and 70 years of age.

Understandably many people in the 60-70 age cohort were concerned, even though the risk of clotting was low. Many older people have a history of clotting, such as deep vein thrombosis, and they wondered if that would put them at higher risk of VITT. This is not the case, because the type of clotting in VITT is very unusual and unlike other clotting disorders. But it is still a concern that worried many.

The AstraZeneca vaccine also performed less well overall than the Pfizer vaccine, giving 62-90pc protection against risk of infection depending on the study, compared to 95pc for the Pfizer/BioNTech vaccine. And then came news that the AstraZeneca vaccine was only marginally protective against infection from the Beta (South Africa) variant, whereas Pfizer/BioNTech was much better. These differences don’t matter a huge amount because AstraZeneca is still providing huge protection against severe disease and death with all variants as far as we currently know, which is what really counts. It’s understandable, though, that these developments made people reluctant when it came to AstraZeneca.

The justification for giving the over-60s the AstraZeneca vaccine based on a lower risk of unusual and rare clotting events is no longer tenable. In Australia, it has been reported that people over 50 have developed VITT. And most importantly, on the HSE’s own website, we have the risk of VITT across age groups. It is 0.65 per 100,000 people, but guess what? It’s the same across all age groups, including those in the 60-64 age bracket. There is no increased risk for younger people at all and older people are not at a decreased risk. These are still very rare events, but they tell us that using decreased risk of clotting as a reason for giving the over-60s the AstraZeneca vaccine doesn’t hold up.

As the vaccine campaign moved down through the ages, another negative aspect reared its ugly head. There was a 12-week gap between the two shots of AstraZeneca, whereas the gap between the Pfizer/BioNTech and Moderna shots was a mere four weeks. Although our perception of time has gone weird because of the pandemic, 12 weeks can feel like a lifetime. Here is a vulnerable group having to wait 12 weeks to be fully vaccinated. And, even more annoyingly, it began to become clear that younger age groups would be fully vaccinated with the other vaccines, while older people just had to wait, grin and bear it.

The unacceptable situation emerged that people in their 60s were not fully vaccinated, while those under 60 — whose risk of dying from Covid-19 is 15 times less — were fully vaccinated. The vaccination policy is therefore perversely providing more protection for people who are less vulnerable than others.

And then the latest sucker punch. In the UK the AstraZeneca vaccine was shown to be less effective against the Delta variant that first emerged in India than the Pfizer/BioNTech vaccine, although again it’s likely to be highly protective against severe disease and death. So not only were vulnerable people in Ireland not fully vaccinated compared to others less vulnerable, but now there’s a variant out there which could harm them.

What has the National Immunisation Advisory Committee (Niac) done about all this — because it must surely be watching this too?

The gap between the first and second shots of the AstraZeneca vaccine has been shortened somewhat to eight weeks. This is a welcome development. And now, four weeks after the first shot of AstraZeneca people are allowed to meet others who aren’t vaccinated (for example, their grandchildren). This should now be reexamined because the Delta variant is out there, against which two shots are needed to provide strong protection.

The over-60s should have a choice of vaccine for their second shot. Several countries are allowing this. Bahrain and the United Arab Emirates have said that people can receive a booster shot of the Pfizer/BioNTech vaccine or the Sinopharm vaccine, regardless of which they had first.

Canada’s own National Advisory Committee on Immunisation said on June 1 that if you’ve had AstraZeneca first, you can have a choice of vaccine for the second shot, including the Pfizer/BioNTech and Moderna vaccines.

Norway said on April 2 that it would offer those who have received a dose of the AstraZeneca vaccine an mRNA vaccine as their second dose. Sweden and Finland have said that people under 65 who have had the AstraZeneca vaccine would actively be given a different vaccine for their second dose.

France has said that people under 55 who have had AstraZeneca first should receive a second dose with Pfizer/BioNTech or Moderna.

Spain’s health minister Carolina Darias said Spain would allow people under 60 who received an AstraZeneca shot first to get a second dose of either the AstraZeneca or Pfizer/BioNTech vaccines.

Niac must be considering all of this. If it is concerned about safety, the committee should read the findings of an Oxford University-led study which found that mixing AstraZeneca and Pfizer/BioNTech was more likely to give rise to mild or moderate common post-vaccination symptoms than either on its own, but that these do not preclude changing vaccines for the second shot. And as regards efficacy, experience with other vaccines (for example the Zabdeno vaccine against the Ebola virus) shows a very strong response.

And a recent study has shown that giving the Pfizer/BioNTech vaccine after the AstraZeneca vaccine gives four times the level of antibodies compared to either used on their own as a double shot. These antibodies neutralise the Alpha (UK) and Beta (South Africa) variants, showing how powerful mixing of different vaccines can be.

To help Niac make this change, it could ask people to sign a waiver to forestall any litigation. People can still go for a second shot of AstraZeneca if they want.

We therefore have a very clear justification for the over-60s and indeed other vulnerable groups, as well as the over-50s, to have a different vaccine after the AstraZeneca vaccine. Get them fully vaccinated as soon as possible, especially with the Delta variant out there. Because they are vulnerable, give them the Pfizer/BioNTech vaccine as a second shot, which on its own justifies this approach.

I predict that mixing and matching of vaccines will become commonplace. It might be especially powerful at keeping new variants that emerge at bay. It’s going to happen anyway, so why not introduce it now for those among us who need it most? They have been messed around enough.

Luke O’Neill is professor of biochemistry in the School of Biochemistry and Immunology at Trinity College Dublin


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