ICMR Study on Mixing Vaccines Has Many Technical Issues: Dr Satyajit Rath

All vaccines go through in-depth research, trials and tribulations, before they are ready for use.

It may take years or decades for a vaccine from discovery and development to approval. But Covid vaccines are the fastest ever created.

The COVID-19 vaccines have had quite a journey since then. Multiple factors like safety concerns, unpredictable supplies, and now, variants have prompted a slew of studies across the world to increase the chances of success or use them judiciously.

The 'mix-and-match' approach – combining two different vaccines is one such idea.

Now, an Indian Council for Medical Research (ICMR) study says that mixing Covishield and Covaxin elicits better immunogenicity, including against the variants, as compared to that produced by two doses of the same vaccine.

'It’s Completely Unsurprising & Expected'

Note that the ICMR study was done by taking advantage of the goof-up in Uttar Pradesh, wherein a group of about 20 people were given two different jabs, in May.

Under the study, 18 people received two doses of two different vaccines, the reaction of which was compared to 40 people who got two doses of Covishield and 40 recipients of two doses of Covaxin.

Goof-up or no goof-up, do the findings of the study bear any good news? How reliable is the analysis? Could it open new possibilities?

"Immunologically, it's completely unsurprising and expected. One, that any such mixing will be perfectly safe, and that any one of these vaccines will serve as a booster for any of the other vaccines," Immunologist Dr Satyajit Rath told FIT.

"The fact remains that one should still collect the evidence and look at the evidence especially before making policy," Dr Rath adds.

So, this isn't something new, and is all just very practical stuff.

Ethical & Technical Concerns

The study titled 'Serendipitous COVID-19 Vaccine-Mix in Uttar Pradesh, India: Safety and Immunogenicity Assessment of a Heterologous Regime', has been published on medRxiv.

Apart from having a really small sample size, Dr Rath says, there are ethical difficulties, too.

"If you look at the preprint, it acknowledges that this was an inadvertent error, but it gives the impression of being a designed study," Dr Rath says.

While the first half of the study title suggests that it was an error, the second half implies this is a formal assessment of safety and immunogenicity of the regime.

Not just unethical, it is unclearly written and has many technical limitations as well.

"It's such a badly written paper...it's very embarrassing," Dr Rath, says.

"Where they are showing antibody level data…the y-axis, which should indicate the antibody level, it’s actually labeled for virus neutralisation," he says.

Dr Rath also says that the antibody level measurement hasn't been properly done.

"Even technically, the data is not particularly accurate."

The study says that the immunogenicity profile against Alpha, Beta and Delta variants in heterologous group was superior, too.

But with 18 samples, there is really no way of saying anything, and their dilution is also not reliable, Dr Rath says.

Since Covishield does not carry the viral N protein, vaccination with it should not have antibodies against the N protein.

"The fact that such anti-N protein antibodies are nonetheless detectable in the Covishield-Covishield group raises the possibility that there may have been extensive unidentified SARS-CoV-2 infection in these study groups. This possibility makes any interpretations of these results even less reliable," Dr Rath says.

The bottom-line is that while it is an interesting preliminary data, it is not particularly reliable.

"We should wait for proper evidence before making policy decisions in the real world," Dr Rath adds.