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Mixing COVID-19 mRNA vaccines: A Q&A with Sunnybrook microbiologist

cartoon doctor gives COVID-19 vaccine to patient

Getting vaccinated is one of the most important things that you can do to protect yourself and your loved ones from COVID-19. With the highly contagious Delta variant circulating in Ontario, getting two doses of COVID-19 vaccine as soon as you are able is integral in helping to prevent a fourth wave and prevent severe illness.

Recently, the National Advisory Committee on Immunizations (NACI) has stated that mixing mRNA vaccines is safe and effective. This is a practice now happening across Ontario.

We asked Sunnybrook Clinical Microbiologist Dr. Rob Kozak to answer some common questions about the COVID-19 vaccines and mixing mRNA doses. Read his answers below.

Dr. Rob Kozak is a scientist and clinical microbiologist who has been involved in COVID-19 research since the virus emerged in Canada. In February 2020, Dr. Kozak was part of a team that received a grant to develop genome sequencing of SARS-CoV-2. In March 2020, he was part of a team that isolated the virus. Learn about his vaccine development work in the University of Toronto Magazine.

Pfizer and Moderna are both mRNA vaccines. Can you tell us a little about the similarities and differences between the two vaccines?

In most ways, Pfizer and Moderna are very similar.

Both vaccines deliver the mRNA that encodes the spike protein of SARS-CoV-2 to cells in your body. The mRNA is a strand of nucleotides, that are like the letters of a word, and serves as the instructions for the cells of your body to make the spike protein of the virus and show it to the immune system, so the immune system can generate antibodies and T-cells that will be protective if you ever encounter the actual COVID-19 virus.

There are some slight differences in the chemical composition of the lipid formulation of each vaccine (these lipids and chemicals are what allow the mRNA to enter your cells), which is why they have different cold storage requirements. But in terms of vaccine efficacy — the most important thing — they both provide excellent protection.

Recommendations originally said people’s second vaccine dose should be the same as the first. If it’s safe, why haven’t we been mixing doses from the beginning?

At the beginning we based all dosing schedules on the data from the Phase 3 clinical trials for efficacy. Then, as the situation evolved and scientists continued to learn more about the vaccines, we adapted based on the best available evidence. For instance, the data showing that a single dose gives good protection and extending the timing between doses would allow many more people to get vaccinated.

Now we have seen more data coming from the UK and Spain showing that mixing doses is safe. Mixing doses isn’t a new concept in the vaccine world. We have actually done it for other infectious diseases and it has been shown to work very well.

What can people expect for an immune response from a mixed vaccine dose? Will it be the same as if they had the same vaccine brand for both doses?

We know in the context of other diseases that when you mix vaccine doses (in scientific jargon this is called “heterologous prime-boosting”) you can get a more robust immune response.

There are ongoing studies looking at this in the context of COVID-19, so we will continue to learn how much this may improve immunity. This could mean longer lasting immunity, or better induction of T-cells, but it will take time to determine this.

One thing is for certain: whether you get two mixed doses or two from the same manufacturer, you will be better protected against the virus than if you just get one shot. Protection against the virus is especially important with the Delta variant now circulating in our communities.

Can you share any other examples of vaccine mixing like this? Has this been done before?

We do this with vaccines for Hepatitis B, Hepatitis A and many other licensed vaccines in Canada. The guidelines from NACI indicate it is fine to use different vaccines from different manufacturers.

Should people wait to receive the same brand mRNA vaccine as their first dose, or get the first one offered to them?

Right now, we are seeing all the right trends as more Canadians get vaccinated, but there are still COVID-19 cases, and the last thing anyone wants is to see another surge.

Vaccination is one of our best tools to prevent another wave. I’ve recommended to my friends and family since the beginning to get the first shot offered to them. This is our best chance at staying safe and having a great summer.

Why is it so important for people to get their second dose of a COVID-19 vaccine as soon as possible?​

We are still seeing COVID-19 cases in Canada, and there is evidence showing that two doses of the vaccine provide better protection against the Delta variant, which is circulating in Ontario. (Some evidence shows that one dose of the COVID-19 vaccine is only 30% effective against the Delta variant).

I think we all deserve to have a great summer spending time with friends and family, and the best way to make sure this happens is to get that second shot as soon as possible.

If people have more questions about mixing vaccine doses, where can they find credible information?

You can find resources and information from the Government of Ontario. Whenever I have questions, I ask my colleagues at Sunnybrook for information.

I would encourage everyone to reach out to their primary health care provider if they need more information.

How can the vaccines be considered “interchangable” if only Pfizer can be used on youth?

Interchangeability and approval in certain age groups are two different things.

In order to get vaccine approval for people in a particular age range (e.g. 12-17 year olds), a research trial must show safety and immunogenicity. This work has been done for the Pfizer vaccine, and regulators have reviewed the data and this is why we can give the Pfizer vaccine to young people.

Similar trials with the Moderna vaccine are ongoing, and I expect we will see results in the not-too-distant future. Once vaccines are approved for a group of people, scientists and vaccine experts will review the data to make sure they can used interchangeably. I would be willing to bet that we will see recommendations in the future indicating it is fine to mix doses for children. After all, this has been done (and shown to be safe!) with other vaccines.

This interview has been edited for length and clarity. 

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