Can you mix and match booster shots?

Approximately 20 months into a global pandemic, the United States continues to struggle with controlling the spread of the COVID-19 virus. Vaccinations to combat COVID-19 were researched and tested, leading to the first batches of the vaccines being distributed and administered initially to at-risk individuals and front line workers in December 2020 before being offered to the wider population. In recent weeks, the U.S. authorities have been debating whether to provide individuals with booster vaccinations to further increase their immunity levels and protection against the virus. President Biden’s administration had suggested that every American should be provided a booster dose of the vaccine, Pfizer or Moderna, as soon as September 20, 2021. However, since the prospect of vaccine boosters has become more widespread, some Americans have asked whether the mixing and matching of vaccines is viable, especially if one’s original vaccine is unavailable as a booster. 

The FDA has stated that a third dose of the recommended booster vaccines, Pfizer and Moderna, will allow increased protection against COVID-19, especially for vulnerable populations. Albert Shaw, MD, Ph.D., a Yale Medicine infectious disease specialist has stated that, “The concept is to prolong protective immunity, particularly if there is evidence that protection is waning after a period of time.” While Americans waited for the FDA’s September 17, decision on booster shots for the general population, clinical trials have been conducted to understand the impact of mixing COVID-19 vaccines. Multiple trials, including the Com-Cov trial, have occurred in the United Kingdom, Spain, and Germany, to evaluate combining two-dose vaccines. The vaccines being tested and mixed include AstraZeneca, Novavac, Pfizer, and Moderna. Early data collected has suggested that one AstraZeneca shot and one Pfizer shot is an effective and safe method for combatting COVID-19. However, researchers noted that when combining the vaccines, there was a higher likelihood that an individual may experience temporary side effects. Lawrence Young, a virologist at the University of Warwick, has stated that this can be due to a stronger immune response that mixing vaccines can produce. The National Institutes of Health (NIH) also began a vaccine trial in June 2021. Experts have stated that the goal of the NIH trial is to determine the advantages and disadvantages of mixing different vaccines as a booster shot. 

Globally, multiple countries have already begun to mix and match vaccines out of necessity, due to the concerns of rare blood clots with the AstraZeneca vaccine. Canada, Germany, France, Spain, and South Korea have all recommended that those who received one dose of an AstraZeneca vaccine should have a second dose of the Moderna or Pfizer vaccine, rather than an additional AstraZeneca shot. The director of the World Health Organization (WHO), Dr. Kate O’Brien, stated that “based on the basic principles of how vaccines work, we do think that the mix-and-match regimens are going to work.” This educated estimation is becoming increasingly accurate, as mixing and matching vaccine research trials have shown positive results. Additionally, the UK Deputy Chief Medical Officer, Professor Jonathan Van-Tam has detailed that mixing vaccine doses can assist in improving flexibility of booster programs, and supporting countries that are experiencing supply issues. Immunologically and historically, it makes sense to provide an additional dose of vaccine with a different platform, as seen with HIV trials and studies.  Given the early results of the research trials, COVID-19 vaccine recipients can feel more comfortable mixing and matching vaccines. However, further research must be completed to verify the efficacy and safety of mixing and matching specific COVID-19 vaccines. 

Regardless of what the U.S. authorities decide regarding a full roll out of booster shots, there needs to be unambiguous messaging that clearly communicates the reasons why boosters are needed, who is recommended to receive them and whether or not vaccines can be mixed or should be matched with the original vaccines. Whereas the main mission of any vaccination program should be to prioritize people getting their first shot, AM’s experience working in communities to build vaccine confidence shows that any booster campaign will face similar challenges to what we are currently experiencing.


AM LLC is currently working nationwide with multiple states and public health agencies on testing, contact tracing, and vaccination programs. Counties, states, or K-12 partners that are interested in partnering with AM for COVID-19 mitigation support should contact Dr. Christopher K Orlea at

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