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

By Varun C. Anipindi

 A new study published in The Lancet by researchers from Oxford University provides more in-depth safety and immunogenicity data to support a “mix-and-match” vaccine strategy, similar to the one currently used in Canada.

Faced with vaccine supply issues and to increase the speed at which the entire population could be immunized, Canada supported a heterologous prime/boost schedule, i.e., a “mix and match” strategy. While these observations were supported by a previous study indicating that the “mix and match” AstraZeneca-Pfizer schedule may be more reactogenic, this new study provides even more details. Health Canada has approved all three anti-COVID-19 vaccines covered in this UK study: the Oxford-AstraZeneca ChAdOx1 (ChAd), Pfizer-BioNTech (BNT) and Moderna (mRNA-1273).

Key points:

  • All vaccine combinations were highly effective in protecting against severe COVID-19, with no vaccine-related adverse events recorded across any of the different vaccine combinations.
  • The AstraZeneca/Pfizer vaccine combination was not inferior to the AstraZeneca/AstraZeneca vaccine regimen.
  • The AstraZeneca vaccine, followed by a Pfizer boost, was associated with increased immunogenicity with respect to anti-spike IgG antibodies and T cell responses compared to the AstraZeneca-AstraZeneca vaccine regimen.

Researchers recruited 975 participants aged 50 or older for their study. Participants were then divided into multiple groups with various vaccine combinations of the AstraZeneca and Pfizer vaccines (AZ/AZ, AZ/Pfizer; Pfizer/Pfizer; Pfizer/AZ). At 28 days post-dose 2, the AZ/Pfizer regimen induced significantly greater levels of anti-spike IgG that also correlated with increased neutralizing antibodies, compared to the homologous AZ/AZ vaccine regimen. T cell responses were also greater in the mixed vaccine schedule versus the homologous AstraZeneca vaccine schedule. Moreover, there were no significant safety concerns raised in all four combinations of vaccine schedules.

Overall, this data supports the use of “mix-and-match” vaccine strategies.


Liu X, Shaw RH, Stuart ASV, et al., Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Lancet, 2021 Aug 6,