by Health Desk Published on June 21, 2021– Updated on May 4, 2022Explainer

May 4, 2022: Recent studies have focused on the "mix and match" approach to COVID-19 booster shots. The idea of using one type of vaccine for the first dose or two and then receiving a booster shot made by a different company has been talked about over the last two years. However, recent data has led a number of health bodies, including the WHO, to endorse the use of mixed vaccines and mixed boosters in people, meaning that someone can get a booster that is a different type of brand than their original shot, and can also mix shots for a first dose depending on the vaccines available.

The World Health Organization (WHO) stance is that you should take whichever vaccine is made available to you first, and that it is safe and effective to mix-and-match different COVID-19 vaccines. This stance is based on studies researching the safety and efficacy of mix-and-matching different vaccines, and is a normal practice is many countries globally/   Scientists believe mixing boosters could actually help enhance the immune system's response to the COVID-19 virus and potentially obtain more protection against severe symptoms, hospitalizations, and deaths as a result of infection.   Several countries have also been allowing residents to mix shots for their initial COVID-19 vaccines in addition to boosters. The World Health Organization (WHO) has stated that "It is safe for you to receive two different COVID-19 vaccines for your first and second dose....WHO considers two doses of any WHO emergency use listings COVID-19 vaccines to be a complete primary series."

The WHO has authorized the following vaccines to receive emergency use listings:

• AstraZeneca/Oxford vaccine
• Johnson and Johnson
• Moderna
• Pfizer/BionTech
• Sinopharm
• Sinovac
• COVAXIN
• Covovax
• Nuvaxovid

The WHO's Strategic Advisory Group of Experts (SAGE) suggested that people who have received two shots of Sinovac of Sinopharm can mix a Pfizer or AstraZeneca shot for the third dose. Studies have also demonstrated that using AstraZeneca's vaccine for the first two shots followed by an mRNA shot is another way to enhance protection.   Right now, more research is being done to understand more about mixing vaccines and boosters which will likely inform its future policies.   Other health bodies globally have also authorized the practice of mix-and-matching vaccines. The United States Centers for Disease Control and Prevention (U.S. CDC), for example, has authorized the use of mixed boosters following full vaccinations in people, meaning that someone can get a booster that is a different type or brand from their original shot. For those who have received Pfizer or Moderna's mRNA vaccines, substituting one for the other for a booster shot has been shown to be effective.    The U.S. CDC also now offers the ability for people who received one or two Johnson & Johnson shots for their initial vaccinations to substitute an mRNA vaccine for their booster.

Aug. 11, 2021: With the emergence of the highly transmissible COVID-19 delta variant, more and more COVID-19 vaccine combinations have been reported, especially with many people taking a booster dose of an mRNA vaccine (Pfizer or Moderna) after the single dose of the Johnson & Johnson’s Janssen vaccine. Several countries in Europe followed up their AstraZeneca shots with Pfizer/ BioNTech or Moderna vaccines. The immune response in patients who received mixed doses seems to be strong, according to available data.

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)
19. CDC Recommends Additional Boosters for Certain Individuals (United States Centers for Disease Control and Prevention)
20. Mixing and Matching COVID-19 Vaccine Booster Doses (United States National Institutes of Health)
21. Episode #54 - COVID-19: Mixed and fractional vaccine doses (World Health Organization)
22. COVID-19 advice for the public: Getting vaccinated (World Health Organization)
23. Coronavirus disease (COVID-19): Vaccines safety (World Health Organization)
24. WHO Experts Recommend Third Booster to Supplement Chinese Vaccines (Health Policy Watch)
25. Copyright-free vaccine bottle photo by Maksim Goncharenok on pexels

Used with Permission from Health Desk, a public health hub that explains emerging COVID-19 science.