COVID-19 vaccine ‘mix and match’: Which combination is better?

• A nationwide cohort study in Sweden has shown ‘mixing and matching’ vaccines is safe, just as the Food and Drug Administration (FDA) has approved a mix and match approach for booster shots in the United States.
• Study shows that having an mRNA COVID-19 vaccine dose after an Oxford-AstraZeneca dose offers better protection against infection than two doses of Oxford-AstraZeneca.
• Until now, scientists have not known whether ‘mixing and matching’ vaccines offers the same or better protection than receiving two doses of the same vaccine.

One of the most impressive scientific developments to come out of the COVID-19 pandemic was the development of effective vaccines in less than a year.

Some of these vaccines, produced by Pfizer and Moderna, used mRNA vaccine technology for the first time. They have potentially laid the path for further vaccine development.

Others, such as Oxford-AstraZeneca, Johnson & Johnson, and Sputnik, have developed vaccines using more traditional viral vector vaccine technology to protect against the virus.

The discovery of the small risk of thromboembolism from the Oxford-AstraZeneca vaccine, alongside variation in vaccine availability, meant that some people have had to receive a different type of vaccine for their first and second dose.

While evidence existed for an immune response among people who received a traditional vaccine followed by an mRNA vaccine, there was no evidence to show whether mixing the two types of vaccine protected against SARS-CoV-2 infection.

‘Gold standard study’ reveals best protection

A nationwide cohort study of 721,787 individuals in Sweden has demonstrated that people who have received an Oxford-AstraZeneca vaccine dose followed by a Pfizer or Moderna vaccine dose have more protection against infection than people who received two Oxford-AstraZeneca doses.

The study, published in The Lancet Regional Health, was the ‘gold standard study’ people had been waiting for, said Professor Monica Gandhi, professor of medicine at the University of California, San Francisco (UCSF), who was not involved in the research.

In an interview with Medical News Today, she said:

“I think it should essentially push any region of the world that is using an adenovirus DNA vector [vaccine to say] that that should be the first dose but the second dose, if at all possible worldwide, should be the mRNA vaccine, because this is the gold standard study.”

Professor Jeff Kwong from the Dalla Lana School of Public Health, University of Toronto, Canada, who was not involved in the research, echoed Prof. Gandhi’s views.

He said: “Evidence from at least three Canadian provinces, Ontario, British Columbia, and Quebec, suggests that it appears that getting one dose of Oxford-AstraZeneca and one dose of an mRNA vaccine appears to be as good as getting two doses of mRNA vaccine in terms of preventing both infection and severe outcomes [such as] hospitalization or death.”

“So, if a country has supplies of both Oxford-AstraZeneca and mRNA vaccines, they might consider giving one dose of each to their population.”

Analyzing publicly available data

Researchers analyzed publicly available data in Sweden to determine how much protection a dose of the Oxford-AstraZeneca vaccine followed by a dose of an mRNA vaccine, either by Pfizer or Moderna, gives against infection.

As the law in Sweden requires that doctors share health records on vaccination and SARS-CoV-2 infection with authorities, researchers from Umeå University could access information on whether people had been vaccinated, with which vaccine, and whether they had received a diagnosis of COVID-19 or required hospitalization afterward.

In total, the researchers gathered data on 721,787 individuals; 430,100 of them had received two doses of the Oxford-AstraZeneca vaccine, and 110,971 had received a dose of Oxford-AstraZeneca followed by an mRNA vaccine dose.

The researchers matched these individuals with an unvaccinated person of the same sex born in the same year and from the same area.

The researchers followed the participants for up to 183 days, from 14 days after the vaccinated people received the second dose to determine if they contracted SARS-CoV-2.

They discovered that unvaccinated people were over 3.5 times more likely to contract a SARS-CoV-2 infection than people who had received vaccinations.

They also found that the:

• Oxford-AstraZeneca vaccine provided 50% protection against infection.
• Oxford-AstraZeneca vaccine followed by a Pfizer vaccine dose was 67% effective against infection.
• Oxford-AstraZeneca vaccine followed by a second dose of Moderna had 79% protection against infection.

Will the US allow ‘mix and match’ vaccines?

The paper’s publication appeared around the same time as the FDA approved a ‘mix and match’ approach for booster shots in the U.S.

This was following the publication of a preliminary report of a federally funded study looking at the immune response and safety of mixing COVID-19 vaccines.

The study concluded that ‘mix and match’ vaccination was safe and induced an immune response, but it did not look at protection against SARS-CoV-2 infection. It states that people who received a Moderna booster after a single dose of the Johnson & Johnson vaccine saw their antibody levels rise 76-fold in 15 days, compared to an increase of just 4 times after an extra dose of Johnson & Johnson.

Dr. Gandhi explained to Medical News Today: “All of these arguments are now swept aside by an actual clinical study that looks at symptomatic infection. […] Essentially, what we were waiting for, was this kind of study.”

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