COVID vaccine interchangeability – what is the evidence?


The latest recommendation from the National Advisory Committee on Immunization (NACI) is that the second COVID-19 vaccination can be administered with a different vaccine product  (NACI, 1 June 2021). Consequently, people who received the AstraZeneca vaccine can be switched to an mRNA vaccine for the second dose. The recommendation was based on concerns about vaccine-induced immune thrombotic thrombocytopenia (VITT) following first and second vaccinations with viral-vector vaccines.

This latest recommendation was based on data from four studies. In the ongoing phase II CoM-Cov trial in the U.K., 830 subjects received a prime vaccine of either the AstraZeneca or Pfizer-BioNTech vaccine followed by the same or the alternative as the boost; the dosing schedule was either 28 days or 84 days (4 treatment groups x 2 dose schedules or 8 treatment groups in total). The primary endpoint was vaccine response (anti-spike Igs) and results are expected later this month.

A secondary endpoint was safety and preliminary results have now been published (Shaw et al. Lancet 2021;397:2043-2046, free full text at Adverse events were more common with the mixed-vaccine regimens. In the group receiving the AstraZeneca vaccine followed by the Pfizer vaccine, adverse events included feverishness (34% vs. 10% for AZ/AZ and 21% for Pfizer/Pfizer); chills (38% vs. 12% for AZ/AZ and 24% for Pfizer/Pfizer); headache (65% vs. 32% for AZ/AZ and 43% for Pfizer/Pfizer); and malaise (54% vs. 17% for AZ/AZ and 36% for Pfizer/Pfizer). There were no reports of thrombocytopenia at 7 days post-boost. Mixing vaccines did not appear to increase the frequency of hematologic and biochemical adverse events.

In the CombivacS trial in Spain, 663 individuals who had received the AstraZeneca vaccine were randomized to a Pfizer boost at >8 weeks or no booster vaccination. Following the second vaccination, antibody titres increased 150-fold at 14 days compared to no change in the control group. The most common adverse events with mixed vaccines were headache (44%), malaise (41%), chills (25%), nausea (11%), and cough (7%). The preliminary results are unpublished but were shown in an online presentation (

NACI also cited a German observational study of 340 healthcare workers published as a preprint (Hillus et al. medRxiv, epublished 2 June 2021; full text at Preliminary results indicated that systemic adverse events were less common with the AZ/Pfizer combination (51.52%) compared to Pfizer/Pfizer (64.78%), although subjects receiving mixed doses were more likely to take prophylactic antipyretics (33.3% vs. 22.6%). Severe systemic reactions were also less common with the combination. Anti-spike IgG positivity at three weeks after boost was similar with AZ/Pfizer and Pfizer/Pfizer (100% vs. 99%).

Additional immunogenicity data were available from the CombivacS trial in a separate publication (Borobia et al. Lancet 2021, preprint 27 May 2021; full text at The AZ/Pfizer combination produced significant elevations in anti-CoV-2 antibody titres as soon as day 7. There were also significant elevations in the spike-specific T cell response (IFN-gamma production) with the boost.

NACI also noted that mixing mRNA vaccines (Pfizer, Moderna) may be considered if the original vaccine product is unavailable or unknown. There are no data on whether vaccines can be interchanged in the case of travellers to Canada who have received other vaccine products not approved by Health Canada. NACI is currently consulting with the Committee to Advise on Tropical Medicine and Travel (CATMAT) to address this issue.

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