The biggest drawback is that deviating from the specified interval used in the Phase 3 trial means that we can’t be confident that the vaccine will work as well in the real-world as it did in clinical trials. And this is a major drawback. At the same time, as a researcher who is not involved in vaccine implementation, vaccine delivery programs in the US seem chaotic at the moment. If this means that the carefully controlled conditions of the Phase 3 trials won’t be replicated anyway, it makes sense to me to administer as many first vaccine doses as quickly as possible even if that means that some people have their boosts deferred. It is still important to strive for two doses of the Pfizer and Moderna vaccines to maximize the likelihood of having protective immunity.

The primary benefit in being able to use different brands of vaccines interchangeably is better coverage in the population, especially if there is a shortage due to manufacturing or distribution. If there is a shortage of one brand, being able to use another brand for the second dose would allow vaccinations to stay on schedule. In support of this, there is evidence from previous studies with other types of vaccines that mixing different brands and types of vaccines is still effective and safe and may even be beneficial. The main drawback is we don’t yet know how the approved COVID-19 vaccines work when mixed, or if mixing them could generate new safety issues or increase the frequency of common reactions to the vaccines like fevers and swelling. Deviating from the regimen used in a Phase 3 clinical trial raises unknowns in both safety and efficacy. However, by approving and rolling out multiple COVID-19 vaccines, vaccine mixing is likely inevitable. Preclinical studies are now in progress to test vaccines in combination.

Historically, mixtures of vaccine types have been used on purpose. Two polio vaccines were eventually used, a live attenuated one and an inactivated one. For a time, they were actually used in combination, priming with the live attenuated vaccine and then boosting with the inactivated vaccine. In further support of mixing different types of vaccines, a phase 3 human clinical trial of an HIV vaccine—consisting of priming with a live attenuated Fowlpox viral vectored vaccine and boosting with recombinant protein vaccine—was safe and, to date, is the only HIV vaccine trial that exhibited some efficacy. The prime-boost regimen using different types of vaccines is an area of intense study and numerous other studies in the lab have shown that when you combine two different types of vaccines, you can get a better response with the combination than using either vaccine alone in a two-dose regimen. The reasons mixing can work are not entirely known, but the findings from these studies provide some confidence that mixing COVID-19 vaccines will not likely be a problem and may even be beneficial.