At first glance, the concept of mixing and matching two different vaccines is perplexing—if not horrifying. Perhaps it’s because we tend to think of vaccines like medicines: we feel like we have to complete the vaccine series by getting two doses of the same vaccine. Otherwise, we feel they might not be as effective.
And perhaps these worries are justified. After all, large-scale studies have only shown these vaccines’ effectiveness when used individually. However, new research is confirming that there are, in fact, significant benefits to mixing COVID-19 vaccines. Those are on both a medical and social level.
The short—and often unstable—supply of vaccines has forced many medical authorities to consider alternatives to the standard vaccine series.
But many of the earliest studies on vaccine mixing were largely caused by concerns over the safety of the Oxford-AstraZeneca vaccine. This particular vaccine has seen rare instances of blood clotting, leading authorities in Canada—and elsewhere—to temporarily halt its use. With many left with just a single dose, switching to another brand seemed like the only option for full immunization.
Trials and Research
Last Monday, a study by researchers from the University of Oxford showed that one dose of Oxford-AstraZeneca with one dose of Pfizer-BioNTech produced a “robust” immune response [1].
Similar results have been found in a German study, where this combination has outperformed two doses of the Oxford-AstraZeneca vaccine based on measured immune response [2]. It is as good as or better than two doses of the Pfizer vaccine [1, 2].
A central cause behind these results could be due to triggering responses through two separate channels, which could provoke a stronger immune response than either one individually. However, it’s unclear whether these results will hold up in large-scale efficacy studies.
The research so far has only measured the direct immune response individuals have when given the vaccine—antibodies, T-cell responses, and so on. What researchers have yet to show is how the mixed vaccine series performs in the real world. A large-scale study, similar to a phase III clinical trial, would be required.
Although we still don’t know much about efficacy, preliminary results for the AstraZeneca/Pfizer combination are fairly promising.
Going forward, the study from the University of Oxford, known as Com-COV, is presently testing other combinations, including with the Moderna and Novavax vaccines [3].
Safety
None of the trials performed with mixed vaccines have reported any severe side effects, though the U.K. Com-COV study did note a slight increase in side effects compared to two doses of the same vaccine [1]. However, because these trials were only performed with a few hundred participants, rare adverse effects may still exist. The risk of this sort of vaccine series could very well be heightened compared to same-vaccine doses.
Overall, individuals and governments will have to decide whether to go ahead with mixed vaccine series despite potential risks. For this reason, some researchers continue to recommend two doses of the same vaccine [3].
However, the growing priority is likely getting as many people fully vaccinated as possible. And if governments can do that will mixed vaccine programs, they could overcome certain supply challenges between manufacturers.
In early June, the Canadian government updated its recommendations for the mixing of vaccines between doses, giving more flexibility to what individuals can receive. Current guidelines suggest that an AstraZeneca dose can be followed up with either Pfizer or Moderna, while Pfizer and Moderna are themselves interchangeable due to their similar mRNA technology.
For everyone under 18, though, there’s currently not much choice. Though other vaccines are undergoing approval, the government has only approved Pfizer for use for individuals under 18. And as this topic is still developing, more news and guidelines from government agencies are sure to come.
