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Is it safe to mix vaccines?

This article was published on
June 21, 2021

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Recent studies suggest that people receiving a first dose of the AstraZeneca/Oxford COVID-19 vaccine and a second dose of an mRNA vaccine (Pfizer/BioNTech or Moderna) appears to be safe and produces a strong immune response. This method may cause more short-term side effects. Until we have more research about the mixing and matching of other vaccines, this approach is not recommended unless national health agencies have allowed their usage.

Recent studies suggest that people receiving a first dose of the AstraZeneca/Oxford COVID-19 vaccine and a second dose of an mRNA vaccine (Pfizer/BioNTech or Moderna) appears to be safe and produces a strong immune response. This method may cause more short-term side effects. Until we have more research about the mixing and matching of other vaccines, this approach is not recommended unless national health agencies have allowed their usage.

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What our experts say

Mixing some COVID-19 vaccines appears to be safe, and generates a strong immune response. However, this may not be true for all World Health Organization (WHO) approved vaccines.

Recent studies from several countries have shown that giving the AstraZeneca vaccine as a first dose and the Pfizer vaccine as a second dose can produce a strong immune response. However, this combination can also cause more short-term side effects after the second dose.

Most COVID-19 vaccines work by targeting the same spike protein, which means that switching vaccines may work from a biological perspective. The WHO says there is not enough data yet to determine whether some vaccines can be used in place of others, which has caused an increase in research to answer that question.

In the United States, clinical trials are happening to see if mixed vaccines can be used as booster shots in adults that are already fully vaccinated. France and Germany have advised in favor of a mixed vaccine approach in some cases, because those governments no longer recommend the AstraZeneca vaccine for certain age groups. Canada, Finland, France, Norway, Sweden, Spain, and South Korea have also allowed the use of a different vaccine for the second dose if the first dose given was AstraZeneca.

Spain's Combivacs study showed that people who received a first dose of the AstraZeneca vaccine and a second dose of the Pfizer vaccine had a stronger response than patients who received two AstraZeneca doses. Meanwhile, a study by Oxford Vaccine Group's Com-Cov trial showed that people who received mixed vaccine types had more severe side effects. The study has not yet determined the impact of mixing vaccines on the immune system.

Researchers from the National Institutes for Food and Drug Control in China recently tested four different COVID-19 vaccine types in mice and found that rodents who received a first dose of an adenovirus vaccine followed by a second dose of a different type of vaccine had a stronger immune response. These outcomes did not occur when the types of vaccines were given in reverse order.

AstraZeneca is currently studying whether or not a first dose of its vaccine and a second dose of the Sputnik V vaccine can help boost immune response. Sinovac and Sinopharm vaccine manufacturers have recently announced that they are considering research on combining those vaccines with doses from other companies.

Mixing tested and approved vaccine combinations may help ease supply chain pressures, boost immune system responses, give broader her immunity, reduce the emergence of new variants, and produce stronger and longer lasting protection. Again, this depends on the specific combination, and mixing non-approved vaccines may lead to negative health impacts or reduced effectiveness.

Mixing vaccines from different manufacturers for specific diseases has been done in the past for influenza, hepatitis A, and other illnesses, but it started with HIV research. Sometimes this option must be taken due to limited supplies, manufacturing delays, recent data about side effects that need to be investigated, and other reasons. One example is Johnson & Johnson's ebola vaccine which uses a mixed-dose approach by administering an adenovirus vaccine in the first dose and a poxvirus vector vaccine in the second.

Context and background

Canada recently recommended combining a first shot of the AstraZeneca vaccine with a second shot of Pfizer or Moderna in certain situations. The guidance suggested that people who received an mRNA vaccine as their first shot (Pfizer or Moderna) should be offered the same vaccine for their second dose. If the original version isn't available, the guidance suggested, then the other mRNA vaccine should be used.

This guidance comes after Canada's public health agency considered a small risk of severe blood clots and low platelets with the AstraZeneca vaccine and new data on immune responses generated when the AstraZeneca vaccine is followed by a dose of the Pfizer vaccine.

The decision was based on recent studies from the United Kingdom, Germany, and Spain. Evidence suggests that an AstraZeneca shot followed by a dose of the Pfizer vaccine had a strong safety profile, despite the potential for more immediate side effects. The data suggests that this approach may boost the immune response of vaccine recipients.

Several countries and companies have looked at the potential for mixing vaccines after reports of the AstraZeneca vaccine being linked to a very rare risk of blood clots.

There are more than ten COVID-19 vaccines being used around the globe now and 1.2 million doses have already been administered, but not all have been approved by the WHO and they may be unsafe to mix unless national health agencies have given guidance about specific combinations.

Resources

  1. Interchangeability of Authorized COVID-19 Vaccines (Public Health Agency of Canada)
  2. PDF [465 KB] Figures Save Share Reprints Request Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data (The Lancet)
  3. Mix-and-match COVID vaccines trigger potent immune response (Nature)
  4. Comparing COVID-19 Vaccine Schedule Combinations (University of Oxford)
  5. Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates (Emerging Microbes & Infections)
  6. Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity (medRxiv)
  7. Canada recommends mixing and matching AstraZeneca, Pfizer and Moderna COVID-19 vaccines (CBC)
  8. Reactogenicity and Immunogenicity of BNT162b2 in Subjects Having Received a First Dose of ChAdOx1s: Initial Results of a Randomised, Adaptive, Phase 2 Trial (CombiVacS) (Preprints with The Lancet)
  9. Is it safe to mix and match COVID-19 vaccines? (Gavi: The Vaccine Alliance)
  10. Factbox: Countries weigh 'mix and match' COVID-19 vaccines (Reuters)
  11. Mixing COVID-19 vaccine doses leads to more reactions, study finds, which may be 'first sign of success' (CBC)
  12. Bahrain offers Pfizer booster for some who got Chinese shots (The Washington Post)
  13. Spanish study finds AstraZeneca vaccine followed by Pfizer dose is safe and effective (Reuters)
  14. Five things to know about: Mixing and matching coronavirus vaccines (Horizon: The EU Research & Innovation Magazine)
  15. FAQ: Where Do Countries Stand on Mixing Vaccines? Is It Safe? (The Quint)
  16. Philippines to study mixing Sinovac with other COVID vaccines (Nikkei Asia)
  17. COVID-19: You can now take Pfizer vaccine after two doses of Sinopharm in Abu Dhabi (Zawya by Refinitiv)
  18. Why mixing vaccines could help boost immunity (MIT Technology Review)

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