This evidence synthesis has been compiled by members of the CITF Secretariat and does not necessarily represent the views of all CITF members.

By Mercedes Yanes Lane

The Health Institute Carlos III in Spain presented preliminary results of their ‘mix and match’ trial using the Oxford Astra Zeneca and Pfizer-BioNTech COVID-19 vaccines. The report describes a high immunogenic response with the combined use of vaccines, compared to people who only received one dose of AstraZeneca. Safety and reactogenicity also appeared similar in people who received two doses of the same vaccine1.


Key points:

  • Individuals who had received a first dose of AstraZeneca further increased their immune response to SARS-CoV-2 after receiving a dose of the Pfizer COVID-19 vaccine.
  • Receiving a dose of Astra Zeneca and then a dose of the Pfizer COVID-19 vaccine appears safe with mild to moderate side effects.


In response to safety concerns, as well as vaccine supply shortages, countries are looking towards using different vaccines as a second dose. This strategy is known as a heterologous prime and boost, as opposed to a homologous vaccination scheme2, but is commonly being referred to as ‘mixing and matching’.

The report (in Spanish), presented by The Health Institute Carlos III, outlines the CombivacS randomized clinical trial which enrolled 673 people who had received one dose of the AstraZeneca vaccine. Among them, 441 participants received a second dose of the Pfizer COVID-19 vaccine, while 232 participants remained as controls and did not receive a second dose. The immunological effects of mixing and matching vaccines were studied measuring antibodies against the receptor binding domain, the trimeric spike protein, and the neutralization capacity of antibodies. In the group with a first dose of AstraZeneca and Pfizer for the second dose, antibody levels were 150 times greater after the second dose – an increase evident as early as seven days after the second dose. For the control group, antibody titres remained the same. For those in the ‘mix and match’ group, antibodies against the trimeric spike protein also showed a high increase and there was a 7-fold increase in neutralization capacity: higher than what has been described for two doses of the same vaccine. Side effects and reactogenicity in the ‘mix and match’ group were similar to that observed in homologous vaccination strategies, with mild to moderate symptoms appearing after vaccination.

The lead scientists for this trial warn that it is not clear how these results compare to trials in which two doses of mRNA vaccines were given. There are many differences between studies and the only way to directly compare is in a randomized trial. Added to this, more information is needed on the effects of a third or booster dose. The authors also did not measure the response to two doses of AstraZeneca vaccine as a comparison/control group.


The Canadian situation

Canada is among the countries considering using a mix and match strategy. The COVID-19 Immunity Task Force (CITF) and the Vaccine Surveillance Reference Group (VSRG) recently announced support for a new nation-wide study that will look at the effects of ‘mixing-and-matching’ approved COVID-19 vaccines in adults. The study, entitled “Mix and match of the second COVID-19 vaccine dose for SAfety and ImmunogeniCity,” or MOSAIC, will assess the safety and effectiveness of using two different COVID-19 vaccines for the first and second dose, as well as the effects of increasing the interval between doses.  This study will provide Canadian decision makers with the information required to move forward in the COVID-19 vaccine era, given this team will study the Canadian vaccine reality.3 Other countries considering mixing and matching different vaccines include:  China, Finland, France, Norway, South Korea, Spain, Sweden, the UK, and the USA.4



  1. Instituto de Salud Carlos III. El uso combinado de las vacunas de AstraZeneca y Pfizer contra el SARS-CoV-2 ofrece una potente respuesta inmunitaria. ISCIII. 2021 May 18.
  2. Callaway E. Mix-and-match COVID vaccines trigger potent immune response. 2021 May 19. doi: 10.1038/d41586-021-01359-3.
  3. New Canada-Wide Research to Study Mixing-and-Matching COVID-19 vaccines. Available at
  4. Factbox: Countries weigh ‘mix and match’ COVID-19 vaccines. 2021 May 24. Available at