Combined or mixed COVID-19 vaccine schedules are currently not recommended in Australia. More information relating to safety and efficacy is required.


With the emergence of variant COVID-19 strains, global vaccine supply issues, and the need to rapidly immunise the population, a number of clinical trials are currently underway investigating the option of “mixed schedules” using different brands of COVID-19 vaccines (these trials are outlined below). The concept of using mixed schedules is also known as a heterologous prime-boost regimen, in which a second “boost” dose is a different brand of vaccine to the first “prime” dose. This has been used previously for other vaccination strategies such as for the Ebola virus. These clinical trials will seek to determine the safety of mixed scheduling, as well as examine the immune response when a heterologous prime-boost regimen is used.

Mixed vaccine schedules are currently in use in Canada and several European countries.

Mixed schedules are not currently recommended in Australia, however, they may be warranted in select circumstances, such as:

  • a specific medical contraindication or precaution
  • the need to complete a COVID-19 vaccine course that has been commenced with a brand not available in Australia

For further information refer to ATAGI clinical advice on use of a different COVID-19 vaccine as the second dose in special circumstances.

Current trials investigating the safety and efficacy of mixed vaccine schedules

CombivacS trial (Spain)

This Spanish trial enrolled 663 people who had already received a first dose of COVID-19 AstraZeneca vaccine. Two-thirds (441) of participants were randomised to receive  Comirnaty™ at least eight weeks after their first dose of Astra Zeneca COVID-19 Vaccine. The remaining control group did not receive a booster.

Preliminary results demonstrated  that the combination of COVID-19 Astra Zeneca (prime) and Comirnaty™ (boost) is highly effective in eliciting an immune response. The mixed schedule showed a stronger immune response than most people show following a standard 2 dose course of COVID-19 AstraZeneca. The antibodies generated were able to neutralise the SARS-CoV-2 spike protein in laboratory tests. More information on efficacy in real world situation is required.

Common side effects including headache, chills, mild nausea, cough, and fever, occurred at similar rates to those seen following a standard vaccine schedule. There were no serious adverse events reported.

Com-COV (UK)

Com-COV (Comparing COVID-19 Vaccine Schedule Combinations)  is a UK multi-centre, participant-masked, randomised heterologous prime-boost COVID-19 vaccination study. 830 individuals were allocated to receive either COVID-19 AstraZeneca or  Comirnaty™ as their first dose of COVID-19 vaccine and then allocated either the same vaccine brand or the alternate brand (Comirnaty™ or COVID-19 AstraZeneca) as their second dose. The second dose was administered either 4-12 weeks after the first dose.

Preliminary data on reactogenicity indicates that systemic side effects were reported more frequently following a mixed schedule compared with those who followed the standard vaccine schedule.

Common side effects included fever, chills, fatigue, headache, joint pain, malaise, and muscle ache. Reassuringly, these symptoms were short lived. Results on immunogenicity are pending.

Com-COV 2 (UK)

COM -COV2 (Comparing COVID-19 Vaccine Schedule Combinations – Stage 2) is an extension of COM-COV trial and aims to further investigate the immunogenicity and reactogenicity of a mixed COVID-19 vaccine schedule with additional brands. The trial is currently underway with recruitment starting in February 2021 and has a recruitment target of 1,050 participants. Individuals who have already received a COVID-19 vaccine will be offered an alternate vaccine brand (either COVID-19 AstraZeneca, Comirnaty™, Moderna or Novavax) as the second dose of a mixed schedule. An interval of 8-12 weeks between doses in being investigated.

Saarland University study (Germany)

A German study at Saarland University, enrolled 250 participants and investigated the strength of immune response 2 weeks after completing vaccination. Participants were either given the traditional two dose schedule of COVID-19 AstraZeneca, Comirnaty™ or Moderna COVID-19 vaccines; or a mixed schedule of Comirnaty™ followed by AstraZeneca, or Moderna followed by AstraZeneca. Doses in mixed schedules were administered 9-12 weeks apart.

Preliminary data suggests that a mixed schedule of AstraZeneca followed by Comirnaty™ elicited a greater immune response than a traditional 2 dose course of Comirnaty™, with both vaccine schedules delivering a greater immunogenicity than a traditional course of COVID-19 AstraZeneca. The results are undergoing peer review.

MOSAIC (Canada)

The MOSAIC (Mix and match of the second COVID-19 vaccine dose for Safety and Immunogenicity) study aims to evaluate the immune response of mixed vaccine schedules when administered either 28 days apart or 112 days apart. 1200 participants will be separated into 12 groups, each receiving a course of two COVID-19 vaccines (AstraZeneca, Comirnaty™or Moderna) in various heterogenous and heterologous combinations. Recruitment for this study is currently underway.


Authors: Davina Buntsma (MVEC Immunisation Fellow), Francesca Machingaifa (MVEC Education Nurse Coordinator) and Rachael McGuire (MVEC Education Nurse Coordinator)

Reviewed by: Francesca Machingaifa (MVEC Education Nurse Coordinator) and Rachael McGuire (MVEC Education Nurse Coordinator)

Date: 5 August 2021

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.