There are many vaccines currently in development against COVID-19, and multiple currently being rolled out in countries worldwide. With the demand significantly outpacing supply, some are beginning to wonder whether mixing first and second doses may become a reality. But can you mix COVID-19 vaccines? Is there any research to support doing so?
The Pfizer and Moderna vaccines are mRNA vaccines. mRNA stands for messenger ribonucleic acid. These vaccines teach the body to mount an immune response against the spike protein found on the surface of the SARS-CoV-2 virus (3). When exposed to COVID-19, the body will recognize the virus and has the tools to fight it off.
Both the Pfizer and Moderna vaccines require a second dose of mRNA vaccine given weeks after the first for COVID-19 disease control and prevention. The second dose of the vaccine increases the vaccine’s effectiveness in preventing COVID-19 infection.
Viral vector vaccines
AstraZeneca’s vaccine is a result of a partnership between AstraZeneca and the University of Oxford. The University of Oxford/AstraZeneca vaccine’s technology is different from that found in mRNA vaccines. It is a viral vector vaccine. The vector used in the vaccine is derived from a modified adenovirus that normally infects chimpanzees. Adenoviruses are common viruses that cause cold-like symptoms (5). Part of the COVID-19 spike protein is carried by the modified adenovirus, which triggers immune responses in humans (4).
The Johnson & Johnson / Janssen COVID-19 vaccine has the advantage of being a single-shot vaccine that does not require a second dose. However, this vaccine is currently on hold in the US due to reports of severe blood clots in a small number of people. Because of this, the CDC has recommended pausing its use until scientists have been able to perform a more detailed review of its safety and performance.
Vaccine distribution and shortages
Unfortunately, vaccines are not available equally throughout the world. Most of the approved vaccines have been distributed in the high- and middle-income countries of the United States, the United Kingdom, the European Union, China, and India. More than half of all purchased doses of COVID-19 vaccines going to these countries (7). This leaves other middle- and low-income countries with little access to protection against COVID-19. The current rate of vaccine distribution in low-income countries could possibly only reach 60% vaccinated by 2023 or later (7).
To address this supply issue, some countries have extended the length of time required between the two doses (8). The hope is that the initial dose of the vaccine will provide enough protection while allowing more people to receive the first dose of a vaccine.
On top of these struggles, some vaccine manufacturers warn they may soon face a shortage of raw materials (9). Novavax has experienced a shortage of plastic bags used to grow cells. Pfizer also cut production targets due to raw material quality issues (10).
Because of potential vaccine shortages and the different vaccines that might be available, the possibility of being able to mix COVID-19 vaccines could be another option.
Research for mixing COVID-19 vaccines
Researchers have already begun to study whether or not COVID-19 vaccines can be mixed and matched. A mixed vaccine study is currently being conducted using the Russian COVID-19 vaccine Sputnik V and the AstraZeneca/Oxford vaccine (2). Study participants were initially given a dose of the Sputnik V vaccine, a vector vaccine. Three weeks later, participants receive a booster shot of the AstraZeneca/Oxford vaccine (2). Early efficacy results were promising.
Another clinical trial is studying the safety and efficacy of mixing vaccines. The clinical trial is a non-inferiority study, aimed at determining whether mixing vaccines is worse than non-mixing. Named the Com-Cov study, the initial arm of the study investigated the side effects of mixing and matching the AstraZeneca/Oxford and Pfizer vaccines. The study investigated various vaccine combinations and different lengths of time between doses.
Since the study was initiated, six new arms are being planned. These arms will investigate the effects of mixing the Pfizer vaccine with either the Moderna or Novavax vaccines and the AstraZeneca vaccine with Moderna or Novavax vaccines. Two other arms will compare these results to non-mixing, normal doses of Pfizer/Pfizer and AstraZeneca/AstraZeneca (11).
The investigators hope that the results will help more people to get vaccinated, allow immunization courses to be completed more quickly, and create backup plans if one vaccine runs out of stock.
Currently, the CDC discourages people from the mix and match vaccine approach (12), except in extreme circumstances. A similar stance was taken in England in the Public Health England’s Green Book guidance (8). While mixing vaccines has been a common practice in routine immunizations in the past (13), the COVID-19 vaccines have not had enough clinical study data to support this practice yet.
If the results from the current mix and match COVID-19 vaccines are positive, mixing COVID-19 vaccines may become a common practice in the future. Until enough clinical data has been obtained, people should continue with current advice and public health measures to help protect themselves from infection.
1. Centers for Disease Control and Prevention (CDC). Different Vaccines. [Online] April 13, 2021. [Cited: April 20, 2021.]
2. Cohen, Jon. Should you mix and match COVID-19 vaccines? Scientists are seeking answers. [Online] Science, February 12, 2021. [Cited: April 20, 2021.] https://www.sciencemag.org/news/2021/02/should-you-mix-and-match-covid-19-vaccines-scientists-are-seeking-answers.
3. Centeres for Disease Control and Prevention (CDC). mRNA Vaccines. CDC. [Online] March 4, 2021. [Cited: April 20, 2021.] https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mRNA.html.
4. Knapp, Alex and Rosenbaum, Leah. Here’s What You Need to Know About Astra-Zeneca’s Covid-19 Vaccine. Forbes. [Online] November 23, 2020. [Cited: April 20, 2021.] https://www.forbes.com/sites/alexknapp/2020/11/23/heres-what-you-need-to-know-about-astrazenecas-covid-19-vaccine/?sh=1e00dbe27b3e.
5. Centers for Disease Control and Prevention. Adenoviruses. Centers for Disease Control and Prevention. [Online] [Cited: April 20, 2021.] https://www.cdc.gov/adenovirus/index.html.
6. Mayo Clinic Staff. Different types of COVID-19 vaccines: How they work. Mayo Clinic. [Online] April 16, 2021. [Cited: April 20, 2021.] https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/different-types-of-covid-19-vaccines/art-20506465.
7. Mark McClellan, MD, PhD, et al. Reducing Global COVID Vaccine Shortages: New Research and Recommendations for US Leadership. Durham : Duke Margolis Center for Health Policy, 2021.
8. COVID-19 vaccines: what happened to evidence-based medicine? Quek, Eleanor and Tahir, Hasan. 2, s.l. : British Journal of Hospital Medicine, 2021, Vol. 82.
9. Tapper, James. Global Covid vaccine rollout threatened by shortage of vital components. The Guardian. [Online] April 10, 2021. [Cited: April 20, 2021.] https://www.theguardian.com/world/2021/apr/10/global-covid-vaccine-rollout-threatened-by-shortage-of-vital-components.
10. Staines, Richard. Pfizer cut vaccine production targets because of raw material shortage – reports. pharmaphorum. [Online] December 4, 2020. [Cited: April 20, 2021.] https://pharmaphorum.com/news/pfizer-cut-vaccine-production-targets-because-of-raw-material-shortage-reports/.
11. Covid-19: Moderna and Novavax vaccines to be tested in mixing vaccines trial. Mahase, Elisabeth. n971, s.l. : BMJ, 2021, Vol. 373.
12. COVID-19 in 2021—Continuing Uncertainty. Carlos Del Rio, MD and Malani, MD, MSJ, Preeti. 13, s.l. : JAMA, 2021, Vol. 325.
13. COVID-19 vaccines for low- and middle-income countries. Choi, Edward M. s.l. : Transactions of the Royal Society of Tropical Medicine & Hygiene, 2021, Vol. trab045.
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