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Editor’s Note: COVID-19 Fact Check is a series where we speak to doctors and ask them burning questions about everything related to COVID-19 – from treatments to vaccines and diagnostics.

If Shakespeare were alive, he would say, “To get or not to get, that is not the question” as he rushes people to get vaccinated.

Recently, German Chancellor Angela Merkel got the Moderna vaccine as her second dose after being inoculated with the AstraZeneca-Oxford vaccine.

The German Standing Committee on Vaccination (STIKO) also advised those that got the AstraZeneca vaccine as their first shot, to get a mRNA vaccine as their second, “regardless of their age.”

Canada’s National Advisory Committee on Immunisation (NACI) also recommended mixing vaccines and stated, “an mRNA vaccine is now preferred as the second dose for individuals who have received a first dose of AstraZeneca/Covishield vaccine.”

Spain’s Bioethics Committee told people to get a mRNA vaccine after an AstraZeneca first dose. However, they also said that taking a second dose is all that matters, even if it means taking another dose of the AstraZeneca vaccine. 

In the US, the Food and Drug Administration (FDA) has not yet recommended mixing vaccines. 

A Centers for Disease Control and Prevention (CDC) guidance states that ” COVID-19 vaccines are not interchangeable.” However, under extenuating circumstances, a person can get a different vaccine.  

So where does this bring us on mixing vaccines? Are there any negative side effects? Can we, in India, get two different types of vaccines?

Let’s find out.

Can COVID-19 vaccines available in India be mixed?

Adenovirus and mRNA vaccines are the two types of COVID-19 shots currently in use.

AstraZeneca and Johnson & Johnson vaccines are examples of adenovirus vaccines while Pfzier and Moderna use mRNA. Sputnik V is also an adenovirus vaccine but it is made up of two different shots. Covaxin, on the other hand, is created using inactivated or a dead virus.

These vaccines are completely different and “work in a different way, they are manufactured in a different way, the way they initiate an immune response is also different,” says Dr Rohan Sequeira, Consultant General Medicine, Jaslok Hospital and Research Centre.

This is a dividing factor for health experts. Some are all for mixing the vaccines but others are not yet convinced.

Dr Kate O’Brien, director of the World Health Organisation’s (WHO) vaccine unit told The Associated Press, “Based on the basic principles of how vaccines work, we do think that the mix-and-match regimens are going to work.”

Dr Sunil Jain, Head of Emergency Medicine, Jaslok Hospital & Research Centre also recommends mixing of COVID-19 vaccines.

However, Daniel Altmann, an immunologist at Imperial College London has some different concerns. He told Nature that because the immune system generates a response against the adenovirus, repeated doses of virus-based vaccines might become less effective. mRNA vaccinations, on the other hand, have a tendency to cause more severe adverse effects when doses are increased. The coronavirus pandemic is the first time mRNA vaccines have been licenced and there is no way of knowing what can happen if it is combined with an adenovirus vaccine.

Dr Tushar Tayal, Department of Internal Medicine, CK Birla Hospital, Gurgaon doesn’t advise switching vaccines since the Indian Government recommends completing one’s vaccination course with the same vaccine.

Different studies on mixing vaccines

In order to understand the safety and efficacy of mixing vaccines, various studies are being undertaken and are in different stages of completion. Since we know that these vaccines are safe for people and are effective against SARS-CoV-2, researchers have taken the next step to find out if they play well with each other and invoke a stronger immune response.

Spanish CombivacS trial: 600+ people, who had received one dose of the AstraZeneca vaccine, participated in the trial. Two-thirds of the participants were given Pfizer as their second dose. Preliminary results showed they developed 37 times more SARS-CoV-2 neutralising antibodies and four times more SARS-CoV-2-specific immune cells than those who got only one AstraZeneca dose. 

Com-COV study: 830 volunteers, aged 50 years and older took part in an Oxford-led study to find out if mixing their own vaccine with Pfizer would generate a better immune response. They tried two variations of vaccine schedules – Pfizer followed by AstraZeneca and AstraZeneca followed by Pfizer. After four week, those vaccinated with Astrazeneca followed by Pfizer, four weeks apart, generated a better immune response. They are waiting on results from the 12-week interval trial as well. 

Sputnik V: The Russian-developed vaccine Sputnik V has introduced a new version called Sputnik Light. It is supposed to act as a booster shot and can supposedly be paired with AstraZeneca’s vaccine. Authorities have stated that they will be conducting a study to know how effective the vaccines will be when combined. 

These studies show that, yes, you can mix and match your vaccine. And while some countries are endorsing it, India isn’t. However, there are murmurs of it being a possibility.

What does India say?

Reports have shown that the Centre is looking at studying the effect of mixing shots from two different vaccines. Niti Aayog member VK Paul said, “It [vaccine mixing] is plausible. But there need to be more studies… Our experts are also continuously studying…Scientifically, there is no problem.”

There is a definite possibility that mixing vaccines could either generate a stronger immunity or more antibodies, said AIIMS chief Dr Randeep Guleria. “This is something that has been looked at in the past – giving one vaccine as the priming shot and another as the booster.” 

“One needs more data… a large number of vaccines will be available in the future… Therefore which combination is better is something we don’t know at this time… but yes, initial studies suggest it may be an option,” he added.

Possible side effects of mixing vaccines

Mixing vaccines is not a new technique. The first combined vaccine was created and administered in 1948 to treat individual diphtheria, tetanus, and pertussis (DTP) and was initially used to vaccinate babies and children in 1948.

Even if the above-mentioned studies show it is safe to mix doses, there are always exceptions to the rule. Something we learned with AstraZeneca’s vaccine – thrombocytopenia.

Jain cautions that mixing Pfizer and AstraZeneca could increase the frequency of mild to moderate side effects. However, “these symptoms”, he says, “were short-lived — lasting no longer than a few days — and there were no hospitalisations or other safety concerns.”

Since reports of the AstraZeneca-linked blood clots emerged, many countries have since banned it. People who got their first dose had no other option but to take a different vaccine.

“Mixing and matching allows the completion of immunisation while ensuring safety. Evidence suggested that such mixing ‘has a good safety profile’, “ he added.

Sequeira also said that he hasn’t heard any reports of patients having any adverse effects.

He does say that “there is the possibility that it might actually create a different kind of an immune response.”

Maureen Ferran, Associate Professor of Biology, Rochester Institute of Technology said by mixing and matching vaccines, it could help speed up global vaccination and end the pandemic faster. It could also “trigger a more robust, longer-lasting immune response… better protect people from emerging variants.”