Covishield has Better Response than Covaxin? Dr Kang Explains

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In among one of the first real-world vaccine studies to come out in India, a preprint published in Medrxiv says that Covishield produces significantly higher seropositivity rate and antibody response against the spike protein, in comparison to Covaxin.

The study also says that both vaccines produce a "good immune response."

It's important to note the study is not peer-reviewed yet.

But should those who have taken Covaxin worry? We spoke with Dr Gagandeep Kang, microbiologist from Christian Medical College, Vellore, on the study findings, possible problems with the design and vaccine response. Dr Kang is not part of team that carried out the study.


The Study

Data of 515 vaccinated health care workers, across 21 cities in 13 states, was analysed from across India between January and May 2021. Among them, 425 HCWs had taken Covishield and 90 took Covaxin.

It found that 95 percent of the participants showed seropositivity after the two doses of both vaccines.

"Of the 425 Covishield and 90 Covaxin recipients, 98.1% and 80.0% respectively, showed seropositivity. However, both seropositivity rate and median (IQR) rise in anti-spike antibody was significantly higher in Covishield vs. Covaxin recipient.”

The study found no difference in relation to sex, BMI, blood group and any comorbidities, but people over 60 years or age or those with type 2 diabetes had a significantly lower seropositivity rates.

The research was led by Dr Awadhesh Kumar Singh, consultant endocrinologist, GD Hospital and Diabetes Institute, KolKata, West Bengal.


What Was Unique About the Study?

Dr Kang says that the authors used the same test to study both vaccines, before and after the participants got the jab. Usually when vaccine companies develop vaccines, you can't do a direct comparison of one vaccine and another because the tests to measure immune responses are different.

"Since this was an independent study, they could measure the immune response using the same test," she adds.

The study was examining two different goals - how many people made an immune response, and how good was that response.

"In order to do that, they used an artificial cutoff to check how many people made an immune response, and found that this response was greater in those who took Covishield than those who took Covaxin," she explains.

The second goal was to look for how many people were making antibodies with Covishield and Covaxin, and they found that this measure was "reasonably comparable."

A third more interesting finding that emerged was that those people who had a previous infection before vaccination had an even better immune response compared to those who had just received the two doses. This further corroborates what has been reported from the US in the last two weeks, in that "you get the strongest immune response with a combination of infection and vaccination," says Dr Kang.


What are the issues with the study? 

The study is a pre print, in that it is not yet peer reviewed.

The second important point to keep in mind is that the study "does not measure protection."

Dr Kang says, "the assay that has been done is this study is a binding assay, which measures IgG, it does not measure protection."

Secondly, the cutoff taken to measure whether people are positive or negative is an artificial cutoff. "It does not measure to what we know in real life, even though the company that designed the test will have us believe it does," she explains.

"At the moment we don't know if this cutoff is accurate or not, so these tests do not mean there will be a difference in protection. For that measure, we will need to have a correlate of protection and measure whether the vaccines were performing differently based on that correlate."

She adds that the correlate for measuring protection is more likely to be neutralising antibodies than binding antibodies that were measured in this test.

"Importantly, those who have received Covaxin should not worry - if you don't have antibodies, it does not mean that you don't have protection. We need to wait to get that absolute correlation between antibody level and protection."

Do Inactivated Vaccines Work Differently? 

Dr Raches Ella, Project Lead of COVID-19 Vaccines at Bharat Biotech, the makers of Covaxin, called out the coverage given to the study on Twitter. He said, "Limitation 1: Spike-based IgG's are not appropriate when evaluating Covaxin, which induces broad antibody responses to Spike, N, and M. Recommend live virus neutralization."

We asked Dr Kang that perhaps inactivated vaccines needn't be evaluated only based on spike protein antibodies, since they produce a broad antibody response?

"We don't know if we need all the those antibodies, because spike protein is working very nicely," says Dr Kang, adding that the mRNA vaccines give a very high level of protection even against infection, and just the spike seems to be protective enough.

"So do we need everything that is in inactivated vaccines? We don't know. Is it possible that a combination of all that is in Covaxin will lead to a comparable level of protection through mechanisms that are different from mRNA vaccines? It is certainly possible, we just don't know yet," she says.

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Topics:  covaxin   COVISHIELD   Dr Gagandeep Kang 

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