EXPLAINED: How ICMR Found Mixing Vaccines Is Effective And Safe. Is It An Idea Whose Time Has Come?


The novel coronavirus moves in unpredictable ways, taking on mutations, beating antibodies and defying treatments. The mixing of vaccines has been explored as a strategy for enhancing the immune response to the virus. Now, tracking people who had received doses of both the Covishield and Covaxin shots in a “serendipitous” mix-up, the Indian Council of Medical Research (ICMR) has found that it is not only safe but also provides better immunity.

Why Is ICMR Thanking Luck For The Mixing Study?

It was a mistake that officials said would be punished. A group of about 20 people in UP’s Siddharthnagar district were found in May this year to have received shots of both the vaccines that are the mainstays of India’s vaccination drive.

The group in question were first jabbed with a Covishield shot in the first week of April and then given a Covaxin dose on May 14. As the mix-up came to light, officials said it was an “oversight” as “there are no instructions from the government to administer a cocktail of vaccines”. But it was assured that the recipients had shown no adverse events as a result of getting inoculated with two separate vaccines.

But that became a starting point for ICMR researchers to study the “serendipitous Covid-19 Vaccine-Mix in Uttar Pradesh”, providing them with a ready sample to test whether combining separate vaccines in a two-dose regime was helpful or harmful. And the findings have been positive.

What Has The Study Found?

ICMR researchers sought to compare the immune and safety profile for 18 people who had received the two different vaccines with two groups of 40 people each who had been administered the double-dose regimen of either the Covishield or the Covaxin shot.

The study found no excessive reaction caused by the mix-up, noting “lower and similar adverse events following immunisation in all three groups”, which it said “underlined the safety of the combination vaccine-regime”.

Importantly, the researchers have said that the immunity against the Alpha, Beta and Delta variants of the novel coronavirus in the “heterologous group was superior”. They also noted that this group’s Covid-19 antibody and neutralising antibody response “was also significantly higher compared to that in the homologous groups”.

The researchers said it suggests that “immunisation with a combination of an adenovirus vector platform-based vaccine followed by an inactivated whole virus vaccine was not only safe but also elicited better immunogenicity”. The reference was to the platforms on which the Covishield and Covaxin vaccines are built.

What Kind Of Vaccines Are Covishield, Covaxin?

Covishield, developed by Oxford University and pharma company AstraZeneca, is a viral vector vaccine. How it works is it uses a modified virus — which in the case of Covishield is a chimpanzee adenovirus that causes common cold among the primates but it is tweaked to be harmless to humans — to act as the vector, or carrier, of the genetic code of the spike protein of the novel coronavirus into human cells, following which the immune system trains itself to target the virus. The Sputnik V and Johnson and Johnson vaccine, which too are cleared for use in India, are also viral vector vaccines.

Covaxin, on the other hand, belongs to the category of whole virus vaccines — in this case of the inactivated type — which use the actual virus after it has been engineered to be harmless to humans to trigger an immune response.

Both vaccines, as indeed the other Covid-19 vaccines now out, target the spike protein of the novel coronavirus, which it uses to infect human cells. And that is one of the reasons why experts say mixing different vaccines may not be an issue because all have a similar modus operandi.

Have Other Combinations Been Tried For Mixing Shots?

Multiple studies have now been held in Europe that have mixed the Oxford-AstraZeneca vaccine with the mRNA vaccine made by Pfizer-BioNTech, which is the key shot used by many advanced economies. Researchers have found that mixing these two vaccines leads to an immune response that is at least as good, or even stronger than, two doses of either vaccine.

Nature magazine said these results “are also giving researchers confidence that combining other Covid-19 vaccines, that haven’t yet been tested together, might also work”.

Is Any Country Giving Mixed Shots To Its People?

Quite a few, actually. The list includes the likes of Canada, Bahrain, Bhutan, Thailand, Italy, South Korea, etc. While the approach has been to explore vaccine mixing as a strategy to boost the immune response, especially with new variants emerging, very often the practice has been adopted in the face of medical compulsions.

For example, the likes of Italy and some other European countries okayed the mixing of vaccines following the emergence of rare cases of blood clots among those who had received a first shot of the Oxford-AstraZeneca vaccine. Worried about giving a second dose of the vaccine to vulnerable groups, health authorities said that they could be administered another vaccine instead.

But there may be more pragmatic reasons for mixing shots with reports last month saying that Germany had recommended the strategy as a counter to the Delta variant. In fact, German Chancellor Angela Merkel, 66, received a second shot of Moderna’s mRNA vaccine after a first dose of Oxford-AstraZeneca with a spokesman saying it was her bid to send the message that people should not to be afraid of mixing shots.

Why Are Some Health Authorities Hesitant To Mix Shots?

The World Health Organisation (WHO) has warned about mixing shots, citing the lack of proper and wide-ranging studies that can allow experts to conclude such a practice will be safe and effective. For instance, it is not yet decided what should be the gap between the two doses when separate vaccines are being used and, in any case, the sample groups have been too small so far to allow experts to gauge all possible adverse reactions — some of which can be so rare as to occur in 1 out of million cases.

It is an issue noted by the ICMR researchers, too. Talking about the limitations of their study, they said that “the sample size of 18 participants [in the mixed shot group] is small, the follow up period is only 60-70 days after immunisation with the first dose and baseline serological and immunological data of the participants is not available”. Although the findings underline the safety and effectiveness of mixing vaccines, the researchers said that to “conclusively prove these findings a multicentre randomised control trial needs to be carried out”.

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