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What do we know about the risks of combining more than one of the approved vaccines?

This article was published on
January 4, 2021

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For COVID-19 vaccines that require more than one dose, such as the Pfizer-BioNTech and Moderna vaccines, researchers are still learning about the outcomes of mixing a first dose of one vaccine with a second dose of another. In the clinical trials that have led to emergency authorization of COVID-19 vaccines, combining doses from different vaccines has not yet been tested. This means that scientists do not yet know if combining doses from different COVID-19 vaccine candidates will be as effective or safe. To help provide more data, a clinical trial was announced on February 8, 2021 to begin testing the combination of one dose from the AstraZeneca vaccine candidate with one dose from the Pfizer-BioNTech vaccine candidate. This clinical trial, dubbed Com-Cov, is being led by the University of Oxford and is considered the first in the world to test the combination of different COVID-19 vaccine candidates. Enrollment of 820 participants over 50 years of age is starting, and scientists hope this clinical trial can provide more data and insights by the summer of 2021. It is important to remember that outcomes can potentially vary depending on which COVID-19 vaccines are mixed. For this reason, the first clinical trial testing a combination of the AstraZeneca and Pfizer-BioNTech vaccine candidates may eventually add additional vaccine candidates. As more COVID-19 vaccine candidates become ready for approval, more studies may be needed to understand the outcomes of combining doses between the multiple available vaccine candidates. There are many potential benefits to being able to combine COVID-19 vaccine candidates, which is why scientists are eager for more data to evaluate this. Ramping up COVID-19 vaccine supplies and coordinating distribution remain a challenge, so being able to give vaccines based on availability could mean more people receive the vaccinations faster and more lives are saved. The U.K.'s deputy chief medical officer has said that there may be benefits to having data that could support more "flexible" vaccination programs, since there is currently an insufficient global supply of COVID-19 vaccines. Beyond the logistical benefits, there could potentially be immunological benefits of using two different vaccines to combat the same pathogen in certain cases. For COVID-19 vaccines that are given in two doses, the "prime" dose is followed by a "boost" dose to help stimulate and amplify the body's immune response, with the goal of developing immunological memory to protect against COVID-19 infections in the future. The strategy of using doses from different vaccines is known as "heterologous prime-boost." Some COVID-19 vaccine candidates, like the Russian Sputnik V, have even been designed to use this strategy with the first and second doses containing different viral components. With newer and faster-spreading variants of COVID-19 emerging around the world, some of which could be partially resistant to immune responses triggered by the vaccines, scientists are also planning to investigate whether combining different vaccines can help offer more protection. Multiple COVID-19 vaccine candidates have been developed in record speed to help combat the global pandemic. In order to take full advantage of every tool that is available for pandemic response, scientists are studying the potential of combining doses from different COVID-19 vaccine candidates. As more data becomes available, public health experts and policymakers will be able to make more informed decisions about "mixing and matching" COVID-19 vaccine doses.

For COVID-19 vaccines that require more than one dose, such as the Pfizer-BioNTech and Moderna vaccines, researchers are still learning about the outcomes of mixing a first dose of one vaccine with a second dose of another. In the clinical trials that have led to emergency authorization of COVID-19 vaccines, combining doses from different vaccines has not yet been tested. This means that scientists do not yet know if combining doses from different COVID-19 vaccine candidates will be as effective or safe. To help provide more data, a clinical trial was announced on February 8, 2021 to begin testing the combination of one dose from the AstraZeneca vaccine candidate with one dose from the Pfizer-BioNTech vaccine candidate. This clinical trial, dubbed Com-Cov, is being led by the University of Oxford and is considered the first in the world to test the combination of different COVID-19 vaccine candidates. Enrollment of 820 participants over 50 years of age is starting, and scientists hope this clinical trial can provide more data and insights by the summer of 2021. It is important to remember that outcomes can potentially vary depending on which COVID-19 vaccines are mixed. For this reason, the first clinical trial testing a combination of the AstraZeneca and Pfizer-BioNTech vaccine candidates may eventually add additional vaccine candidates. As more COVID-19 vaccine candidates become ready for approval, more studies may be needed to understand the outcomes of combining doses between the multiple available vaccine candidates. There are many potential benefits to being able to combine COVID-19 vaccine candidates, which is why scientists are eager for more data to evaluate this. Ramping up COVID-19 vaccine supplies and coordinating distribution remain a challenge, so being able to give vaccines based on availability could mean more people receive the vaccinations faster and more lives are saved. The U.K.'s deputy chief medical officer has said that there may be benefits to having data that could support more "flexible" vaccination programs, since there is currently an insufficient global supply of COVID-19 vaccines. Beyond the logistical benefits, there could potentially be immunological benefits of using two different vaccines to combat the same pathogen in certain cases. For COVID-19 vaccines that are given in two doses, the "prime" dose is followed by a "boost" dose to help stimulate and amplify the body's immune response, with the goal of developing immunological memory to protect against COVID-19 infections in the future. The strategy of using doses from different vaccines is known as "heterologous prime-boost." Some COVID-19 vaccine candidates, like the Russian Sputnik V, have even been designed to use this strategy with the first and second doses containing different viral components. With newer and faster-spreading variants of COVID-19 emerging around the world, some of which could be partially resistant to immune responses triggered by the vaccines, scientists are also planning to investigate whether combining different vaccines can help offer more protection. Multiple COVID-19 vaccine candidates have been developed in record speed to help combat the global pandemic. In order to take full advantage of every tool that is available for pandemic response, scientists are studying the potential of combining doses from different COVID-19 vaccine candidates. As more data becomes available, public health experts and policymakers will be able to make more informed decisions about "mixing and matching" COVID-19 vaccine doses.

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What our experts say

Researchers are still learning about the outcomes of mixing a first dose of one vaccine with a second dose of another. In the clinical trials that have led to emergency authorization of COVID-19 vaccines, combining doses from different vaccines has not yet been tested. This means that scientists do not yet know if combining doses from different COVID-19 vaccine candidates will be as effective or safe.

To help provide more data, a clinical trial was announced on February 8, 2021 to begin testing the combination of one dose from the AstraZeneca vaccine candidate with one dose from the Pfizer-BioNTech vaccine candidate. This clinical trial, dubbed Com-Cov, is being led by the University of Oxford and is considered the first in the world to test the combination of different COVID-19 vaccine candidates. Enrollment of 820 participants over 50 years of age is starting, and scientists hope this clinical trial can provide more data and insights by the summer of 2021.

It is important to remember that outcomes may vary depending on which COVID-19 vaccines are mixed. For this reason, the first clinical trial testing a combination of the AstraZeneca and Pfizer-BioNTech vaccine candidates may eventually add additional vaccine candidates. As more COVID-19 vaccine candidates become ready for approval, more studies may be needed to understand the outcomes of combining doses between the multiple available vaccine candidates.

There are many potential benefits to being able to combine COVID-19 vaccine candidates, which is why scientists are eager for more data. Ramping up COVID-19 vaccine supplies and coordinating distribution remain a challenge, so being able to combine available vaccines could mean more people receive vaccinations faster and more lives are saved.

The U.K.'s deputy chief medical officer has said that there may be benefits to having data that could support more "flexible" vaccination programs, since there is currently an insufficient global supply of COVID-19 vaccines.

Beyond the logistical benefits, there could potentially be immunological benefits of using two different vaccines to combat the same pathogen in certain cases. For COVID-19 vaccines that are given in two doses, the "prime" dose is followed by a "boost" dose to help stimulate and amplify the body's immune response, with the goal of developing immunological memory to protect against COVID-19 infections in the future.

The strategy of using doses from different vaccines is known as "heterologous prime-boost." Some COVID-19 vaccine candidates, like the Russian Sputnik V, have even been designed to use this strategy with the first and second doses containing different viral components. With newer and faster-spreading variants of COVID-19 emerging around the world, some of which could be partially resistant to immune responses triggered by the vaccines, scientists are also planning to investigate whether combining different vaccines can help offer more protection.

Multiple COVID-19 vaccine candidates have been developed in record speed to help combat the global pandemic. In order to take full advantage of every tool that is available for pandemic response, scientists are studying the potential of combining doses from different COVID-19 vaccine candidates. As more data becomes available, public health experts and policymakers will be able to make more informed decisions about "mixing and matching" COVID-19 vaccine doses.

Context and background

There are supply chain and logistical challenges when it comes to vaccinating enough people among the general public to reduce COVID-19 transmission. In response, some places like the U.K. have allowed a dose from one COVID-19 vaccine to be substituted for another, when there are issues with availability. Since there is currently limited data on "mixing and matching" COVID-19 vaccine doses, some experts have raised concerns about allowing doses from one vaccine to be interchanged with another.

Regulatory agencies in different countries have different approaches. As of January 21, 2021, the U.S. Centers for Disease Control and Prevention (CDC) guidelines state: "The safety and efficacy of a mixed-product series have not been evaluated. Both doses of the series should be completed with the same product." However, the U.S. CDC guidelines acknowledge that exceptional situations may occur, such as when there is missing documentation on which vaccine a patient received as their first dose and the second dose may depend on availability.

Historically, combining doses from different vaccines is not unprecedented. For example, there have been clinical trials testing the mixing of different influenza (flu) vaccines. European regulatory agencies have approved the combination of different Ebola vaccines, and some experimental HIV vaccine programs have also been trying to combine two vaccines against the same pathogen.

Scientists hope to use data from monitoring vaccination combinations in different countries, along with data from upcoming clinical trials on combining different COVID-19 vaccines, to be able to say more about the efficacy and safety of this "mixing and matching" approach.

Resources

  1. Could mixing COVID vaccines boost immune response? (Nature)
  2. What you need to know about Covid vaccine mixing and matching (The Independent)
  3. Britain to test mixing and matching of COVID-19 vaccines (Associated Press)
  4. U.K. to test mixing COVID-19 vaccines in world-first trial (Axios)
  5. New Covid-19 trial tests mixing two different vaccines for first time (NBC)
  6. Britain Opens Door to Mix-and-Match Vaccinations, Worrying Experts (NYTimes)
  7. Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States: Interchangeability with other COVID-19 vaccine products (U.S. CDC)
  8. A Phase I Safety and Immunogenicity Study of Mix and Match of Licensed Flu Vaccine and Flumist (ClinicalTrials.gov

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