on Jun 02, 2021)Is it safe to take shots of two different Covid vaccines? Are mixed vaccinations less or more protective? Several countries have begun trials to find out while the Indian government said it won’t change its vaccine protocols till mixed vaccinations are backed by science. If the trials succeed, you won’t need to delay your second dose just because a specific vaccine is not available.
Some countries have already allowed such ‘mix-and-match’ vaccinations in emergencies, with early trial results suggesting some combinations are safe and potentially more effective.
What mixing vaccines could look like
All approved vaccines, except Johnson & Johnson, need two doses. Generally, the first dose primes the immune system to recognise the virus and the second boosts the recognition and response to it.
Combining vaccines, say with a first dose of a viral vector vaccine like Oxford-AstraZeneca’s Covishield and a second dose of an mRNA jab like Pfizer-BioNTech, is called ‘heterologous prime-boost’ and it could train the immune system to recognise the virus in more than one way.
Russia’s Sputnik V is a ‘combination’ vaccine by design. The first dose uses a harmless common cold adenovirus (Ad26) to deliver genetic instructions for cells to produce the coronavirus’s spike proteins. The second does it with a different adenovirus (Ad5), to avoid being attacked by the immune system that now recognises Ad26.
The mechanism works — Sputnik V has an efficacy rate of 91.6%, similar to
and Moderna’s mRNA vaccines, although it is a viral vector shot like Covishield.
Some studies on mice have even shown combining vaccines produces a better immune response, but researchers are yet to replicate the results in large human trials.
UK study finds mixing Covishield, Pfizer safe
The Oxford Vaccine Group is conducting the Com-CoV trial in the UK to study a combination of a Pfizer or Covishield first dose followed by a Moderna or Novavax second dose. It will be the largest such study with at least 800 volunteers aged 50 and over enrolled, and space for 1,000 more.
Preliminary results, according to a letter from the researchers published in The Lancet, show a combination of Covishield and Pfizer is likely to produce a stronger immediate physical reaction — soreness or swelling at the site of injection, fever and headaches — after the second dose than two doses of the same vaccine. But these reactions were not severe or long-lasting and there were no other safety concerns.
However, it’s unclear if the combination affects efficacy. More data is expected later this month.
“If we can show that these mixed schedules generate an immune response that is as good as the standard schedules, and without a significant increase in the vaccine reactions, this will potentially allow more people to complete their Covid-19 immunisation course more rapidly,” said Dr Matthew Snape, chief investigator for the study, in an interview with BBC in April.
Could combining vaccines improve immune response?
Some experts say mixing vaccines that target different parts of the virus can better prepare the immune system against a wider range of threats, including new variants.
In a Spanish study involving more than 600 people, 400-odd received a Covishield first dose followed by a Pfizer shot after 8 weeks. They produced a markedly higher level of antibodies than the others, but it remains unclear if the Covishield-Pfizer mix is more effective than two Pfizer doses.
“Individually, these vaccines have proven to be safe and theoretically there should be no safety concern. … Immunologically, the principle is that you prime with one dose and the other boosts it. The key question that needs to be answered would be whether mixing would affect efficacy,” says Dr V Ravi, a virologist and member of the Department of Biotechnology’s expert committee on vaccines, in an interview with TOI.
But for countries faced with vaccine shortages, the primary impetus for mixing shots is logistics, not efficacy. In India, for instance, having multiple safe combinations of vaccines could help ramp up immunisation efforts.
“It will give flexibility to use whatever vaccine is available. Remember, the regulator gave its nod for the same vaccine in two doses, so a bridging trial would be really necessary. So the data — whether it is done in India or outside — has to be produced before the regulator here,” Dr Ravi added.
Countries that allow mixing
The UK, Germany and France have already allowed combining vaccines in ‘exceptional situations’ with several trials, mostly for older populations, underway to better understand the effects. The US and UK have warned against mixing doses unless unavoidable.
In Europe, safety concerns surrounding Covishield prompted Germany and France to recommend younger people who’ve received Covishield first get an mRNA second dose. Other countries are awaiting trial results before officially recommending mixing.
Some experts say mixing might be necessary in the long run if the virus mutates into new variants or if limited immunity from a two-dose vaccine requires a booster sometime next year.
With inputs from Chethan Kumar
