What You Need to Know about Mixing COVID-19 Vaccines

Farheen Khan, (Hons) B.Sc. (Biochemistry) [Get Well Clinic]

As we enter summer 2.0 of the COVID-19 pandemic (and hopefully the final summer as well), Canadians have been preparing to receive their second COVID-19 vaccine dose. To recap, most Canadians have already received their first dose of one of three COVID-19 vaccines: Pfizer-BioNTech (mRNA technology), Moderna (mRNA technology, or Oxford-AstraZeneca (adenoviral vector technology). Though there have been a lot of questions regarding the second dose, the most common ones have been regarding mixing vaccines. If you find yourself wondering whether it is okay to mix any of the available COVID-19 vaccines, please continue to read on as this article may answer some of your questions.

Mixing Oxford-AstraZeneca and a mRNA vaccine (Pfizer-BioNTech or Moderna)

According to the National Advisory Committee on Immunization (NACI), “an mRNA vaccine is now preferred as the second dose for individuals who received a first dose of the AstraZeneca/COVISHIELD vaccine, based on emerging evidence of a potentially better immune response from this mixed vaccine schedule and to mitigate the potential risk of VITT [Vaccine-Induced Immune Thrombotic Thrombocytopenia] associated with viral vector vaccines. People who received two doses of AstraZeneca/COVISHIELD vaccine can rest assured that the vaccine provides good protection against infection and very good protection against severe disease and hospitalization.”1

The Com-COV study in the United Kingdom is a multi-centre, participant-masked, randomized vaccine study in which participants aged 50 and over (820 participants in total) were given either two doses of the Oxford-AstraZeneca vaccine, two doses of the Pfizer-BioNTech vaccine, a dose of the Oxford-AstraZeneca vaccine followed by a dose of the Pfizer-BioNTech vaccine, or a dose of the Pfizer-BioNTech vaccine followed by a dose of the Oxford-AstraZeneca vaccine, 28 or 84 days apart (4 weeks or 12 weeks respectively).2–4 Patients were asked to self-report local solicited adverse effects (i.e., pain, tenderness, redness, etc.) and/or systemic solicited adverse effects (i.e., fever, chills, muscle pains, headache, etc.) in e-diaries for seven days post-vaccination for both, the first and second dose.2,4 Preliminary findings thus far have indicated that participants who received two heterologous vaccines were more likely to experience mild to moderate adverse effects (fevers, chills, fatigue, headache, joint pain, malaise, muscle aches) in the first 48 hours post-immunization compared to participants who received two doses of the same vaccine.3 No hospitalization was reported due to the adverse effects.3 The hematology and biochemistry profiles of participants who received two doses of the same vaccines and of those who received two doses of different vaccines were similar.3 Nonetheless, to determine the overall effectiveness of mixing Oxford-AstraZeneca and Pfizer-BioNTech vaccines, more data is needed; the primary immunological outcomes are expected later this month (June 2021).3 Furthermore, the Com-COV2 study (also conducted in the United Kingdom) is expanding the Com-COV study by incorporating Moderna and Novavax vaccines as second-dose candidates after a first dose of either the Oxford-AstraZeneca or Pfizer-BioNTech vaccine.3,5

The CombivacS study in Spain is a comparative and randomized study consisting of participants aged 18-59 (673 participants in total) who had already received a dose of the Oxford-AstraZeneca vaccine at least eight weeks prior to the commencement of the trial.6–8 Of these participants, 441 participants were randomly selected to receive a dose of the Pfizer-BioNTech vaccine, while the remaining participants did not receive a second dose (making the control group).8 The immune response between the two groups were evaluated 14 days after participants in the experimental group had been vaccinated.6,8 Participants were asked to report any adverse effects in an e-diary.8 Preliminary results have demonstrated that the Pfizer-BioNTech booster resulted in a greater production of antibodies capable of recognizing and inactivating the SARS-CoV-2 virus than before (150 times greater) – an effect that was already evident one-week post-vaccination.7,8 Participants of the control group demonstrated no change in antibody levels.7,8 Scientists have even stated that “the antibody response to the Pfizer boost seems to be even stronger than the one most people generate after receiving two doses of the Oxford-AstraZeneca vaccine.”7 No severe side effects were reported, but common side effects including headache, malaise, chills, mild nausea, mild cough, and fever were reported in the first two-three days post-vaccination.8 No hospitalization was reported due to the adverse effects.8

Preliminary findings from a study conducted in Germany (that has not yet been peer-reviewed) have also demonstrated greater antibody production and protection against SARS-CoV-2 variants in participants who received a dose of the Oxford-AstraZeneca vaccine followed by a dose of the Pfizer-BioNTech vaccine, compared to participants who received two doses of the Oxford-AstraZeneca vaccine only.9

Mixing Pfizer-BioNTech and Moderna

No studies have investigated the effects of mixing the two mRNA vaccines. NACI however, states the following:

“Individuals who received a first dose of an mRNA vaccine (Pfizer-BioNTech, Moderna) should be offered the same mRNA product for their second dose. If the same product is not readily available, or the product used for the first dose is unknown, another mRNA vaccine is considered interchangeable and should be used to complete the series.”1

“Currently, no data exist on the interchangeability of COVID-19 mRNA vaccines. However, the spike proteins encoded by either of the authorized mRNA vaccines are stabilized in the same manner to remain in the pre-fusion conformation, though other vaccine components like the lipid nanoparticle and the mRNA sequence may be different. At this time there is no reason to believe that mRNA vaccine series completion with a different authorized mRNA vaccine product would result in any additional safety issues or deficiency in protection.”10

To learn more about the different COVID-19 vaccines, please ensure to read the following two articles:



If you have any further questions regarding the second dose of COVID-19 vaccines, please reach out to your healthcare practitioner.

As the city begins to open up again, providing us with a sneak peak of the pre-COVID-19 life, please book your second-dose appointments as soon as you are eligible. Our fight against this pandemic is not over just yet with the highly contagious delta variant still being of great concern. However, if we all play our role, socially distance, wash our hands, and get vaccinated as soon as possible, we can surely win through the rest of our fight.



(1)        Canada, P. H. A. of. NACI COVID-19 vaccine statement, June 17, 2021: Summary https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-covid-19-vaccines/summary-statement-june-17-2021.html (accessed 2021 -06 -21).

(2)        About Com-COV1 https://comcovstudy.org.uk/about-com-cov1 (accessed 2021 -06 -21).

(3)        Shaw, R. H.; Stuart, A.; Greenland, M.; Liu, X.; Van-Tam, J. S. N.; Snape, M. D. Heterologous Prime-Boost COVID-19 Vaccination: Initial Reactogenicity Data. Lancet Lond. Engl. 2021, 397 (10289), 2043–2046. https://doi.org/10.1016/S0140-6736(21)01115-6.

(4)        Lambe, T. Com-COV Protocol Date and Version No: V7.0 08-June-202. Univ. Oxf. 83.

(5)        About Com-COV2 https://comcovstudy.org.uk/about-com-cov2 (accessed 2021 -06 -21).

(6)        CombivacS « EpidemiXs Studies https://studies.epidemixs.org/en/proyecto/covid-study-vaccine-dose/ (accessed 2021 -06 -21).

(7)        Mix-and-match COVID vaccines trigger potent immune response https://www.nature.com/articles/d41586-021-01359-3 (accessed 2021 -06 -21).

(8)        El uso combinado de las vacunas de AstraZeneca y Pfizer contra el SARS-CoV-2 ofrece una potente respuesta inmunitaria https://www.isciii.es/Noticias/Noticias/Paginas/Noticias/Presentaci%C3%B3n-resultados-preliminares-CombivacS.aspx (accessed 2021 -06 -21).

(9)        Barros-Martins, J.; Hammerschmidt, S. I.; Cossmann, A.; Odak, I.; Stankov, M. V.; Ramos, G. M.; Dopfer-Jablonka, A.; Heidemann, A.; Ritter, C.; Friedrichsen, M.; Schultze-Florey, C.; Ravens, I.; Willenzon, S.; Bubke, A.; Ristenpart, J.; Janssen, A.; Ssebyatika, G.; Bernhardt, G.; Münch, J.; Hoffmann, M.; Pöhlmann, S.; Krey, T.; Bošnjak, B.; Förster, R.; Behrens, G. M. N. Humoral and Cellular Immune Response against SARS-CoV-2 Variants Following Heterologous and Homologous ChAdOx1 NCoV-19/BNT162b2 Vaccination. medRxiv 2021, 2021.06.01.21258172. https://doi.org/10.1101/2021.06.01.21258172.

(10)      Canada, P. H. A. of. Recommendations on the use of COVID-19 vaccines https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-covid-19-vaccines.html (accessed 2021 -06 -21).



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