Heterologous COVID-19 mRNA vaccine schedules and resources for health care providers

Advisory Alert

June 21, 2021

*Cette information est seulement disponible en anglais.

To: Health Care Providers


Interchangeability of COVID-19 vaccines

This Advisory Alert provides information on the interchangeability of COVID-19 mRNA vaccines as well as a Q and A resource to assist health care providers in their discussions on mixing mRNA vaccines to complete the COVID-19 vaccination series.

Heterologous mRNA COVID-19 vaccine schedules

On June 17, 2021, the National Advisory Committee on Immunization updated their statement on the interchangeability of authorized COVID-19 vaccines. Individuals who received a first dose of an mRNA vaccine (Pfizer-BioNTech or Moderna) should be offered the subsequent dose with the same mRNA product, if the same product is readily available[i]. If the same product is not readily available, or the first dose product used is unknown, another mRNA vaccine recommended for that age group should be used to complete the series.

When mixing mRNA vaccines, the minimum dosing interval to complete the series is determined by the product monograph of the first dose product. This means a minimum of 21 days for those who had a first dose of Pfizer-BioNTech and a minimum of 28 days for those who had a first dose of Moderna.

Individuals who received a first dose of a viral vector vaccine (e.g. AstraZeneca vaccine), may choose to complete the series with AstraZeneca or an mRNA vaccine. In their June 17 statement, NACI recommends that an mRNA vaccine is now preferred as the second dose for individuals who received their first dose of AstraZeneca/COVISHIELD vaccine. This is based on emerging evidence of potentially better immune response from the mixed vaccine schedule and to mitigate the potential risk of VITT associated with viral vector vaccines. For more information on heterologous mRNA vaccine schedule and the AstraZeneca or other viral vector vaccines, please see our Advisory Alert dated June 3, 2021.

Evidence for vaccine interchangeability

Heterologous vaccine schedules are not new. Similar vaccines from different manufacturers can be interchanged when vaccine supply or public health programs change. The Pfizer-BioNTech COVID-19 vaccine and the Moderna COVID-19 vaccine have very similar mechanisms of action. Current evidence supports that combining different mRNA vaccines that induce an immune response will lead to robust protection.

With the COVID-19 Delta variant spreading throughout Ontario, it is more important than ever to complete the vaccine series and boost immune response. Emerging evidence shows that there is lower effectiveness of one dose, compared to two, against the Delta variant. Individuals must complete the vaccine series with two doses to improve vaccine effectiveness.

Informed consent and Q&A resource

Patients should understand which product they are receiving for their second dose. They should be able to ask questions prior to vaccination and understand the risk of delaying their second dose if they choose to wait for a product. All patients must provide informed consent for interchanging or mixing mRNA vaccine schedules.

The Ministry of Health’s newest Q&A for Health Care Providers on Heterologous COVID-19 mRNA Vaccine Schedules provides common questions and answers on the mixing and interchangeability of mRNA COVID-19 vaccines. This resource can be used to facilitate the decision-making process when discussing second dose options with your patients. Evidence supporting the mixing of mRNA COVID-19 vaccines as well as the importance of getting as second dose are outlined within the document.

Additional information

For additional information on the COVID-19 vaccines, as well as our sample medical directives for Pfizer BioNTech COVID-19 Vaccine  and Moderna COVID-19 Vaccine, please visit Public Health’s COVID-19 vaccine webpage.


Original Signed By

Dr. Penny Sutcliffe
Medical Officer of Health and Chief Executive Officer

NOTE: All Advisory Alerts are found on our website.

[i] Readily available – easily available at the time of vaccination without delay or vaccine wastage.

This item was last modified on June 21, 2021