Study finds Covishield produces more antibodies than Covaxin, but scientists point out serious flaws with the preprint

A head-to-head evaluation of immune responses to spike protein after the first and second dose of Covishield and Covaxin in 515 health-care workers show that both vaccines elicited good immune responses after two doses. Higher seropositivity rate and higher median antibody titer values are seen for Covishield compared with Covaxin. However, the preprint has several problems.

A head-to-head evaluation of immune responses to spike protein after the first and second dose of Covishield and Covaxin in 515 health-care workers aged above 18 years show that both vaccines elicited good immune responses after two doses.

The seropositivity rates and the median antibody titre against spike protein was “significantly higher” in those vaccinated with Covishield compared with Covaxin, according to a preprint posted in medRxiv. Preprints are yet to be peer-reviewed and published in scientific journals.

The multi-site study undertaken in India and led by Dr. Awadhesh K. Singh, Consultant Endocrinologist, G. D Hospital & Diabetes Institute, Kolkata, evaluated the immune responses 21 days or more after the first and second dose of both vaccines in health-care workers who have not been infected as well as those who have recovered from COVID-19. Only those who have recovered from COVID-19 more than six weeks before the first dose were included in the study.

Of the 515 health-care workers included in the study, 425 received Covishield while 90 were administered Covaxin,

The study found that 98.1% and 80.0% of health-care workers who received Covishield and 90 Covaxin, respectively, showed seropositivity. However, those who received Covishield elicited higher antibody responses antibody against the spike protein compared with Covaxin.

In those who were not previously infected, after the first dose, the median antibody titter against the spike protein was 55 AU/mL for Covishield, while it has just 5 AU/mL for Covaxin. After the second dose, the antibody titter increased to 115 AU/mL for Covishield, while it was just 20 AU/mL for Covaxin.

The higher median antibody titre value for Covishield compared with Covaxin might only mean that the protection offered by Covishield might last longer than Covaxin, says Dr. Chandrakant Lahariya, an epidemiologist and public health specialist. “The higher median antibody titre value does not mean higher protection,” Dr. Lahariya says.

Also, Covaxin, which uses the whole inactivated virus, is more likely to produce antibodies to other antigens of the virus. But for the study, only the antibodies specific to the spike protein was used for comparison as it is the only one common to both vaccines.

Those who have recovered from COVID-19 showed far higher median antibody titre values compared with those who have not been previously infected.

In the case of those who have recovered from COVID-19, the median antibody titre of 400 AU/mL after the first dose of Covishield did not increase after the second dose. But in the case of Covaxin, it increased from 260 to 308 AU/mL.

Problems with the study

Immunologist Dr. Satyajit Rath, formerly with the National Institute of Immunology, Delhi and now a visiting faculty at IISER Pune points out serious shortcomings with the preprint. In the case of those without previous infection, the median antibody titre value is 20 AU/mL for Covaxin after the second dose, though the range is between 51-125. “We would expect the median value to be within the given range. So how is the median value less than the lower limit,” asks Dr. Rath.

In the case of Covishield, the median antibody titre value of 115 falls within the range of 75.8 and 199.3.

The second problem cited by Dr. Rath is the 15 AU/mL value used to calculate the seropositivity rate. “We do not yet know the minimum antibody titre value that offers protection in the case of the spike protein. The 15 AU/mL value chosen is arbitrary,” says Dr. Rath. Professor of Microbiology at CMC Vellore Dr. Gagandeep Kang agrees with Dr. Rath. According to the preprint, the 15 AU/mL cut off for seropositivity was based on the value indicated by the kit manufacturer.

Dr. Rath also says both for individuals who have previous infection and those who are virus naïve, the median antibody titre value of those who are found to be seropositive is not known. The median values given are for the total number of individuals in both groups (with previous infection and virus naïve) immaterial of the seropositive status.  

Dr. Kang points out another serious flaw with the the preprint. The median antibody titer value is the same as the upper limit of the range in the case of those with previous infection. The median value for Covishied after one dose is 400 while the range is 298-400. In the case of Covaxin, the median titre value is 260 while the range is 214-260. After the second dose, the median titre value is 400 for Covishield while the range is 278-400; for Covaxin, the median value is 308 while the range is 233-308.

Also, the sample size of 96 participants — 93 without previous infection and three individuals who have recovered — who received Covaxin is too small a size to arrive at any definite conclusion.

Finally, while the study says 515 healthcare workers were included in the study, the total number of participants mentioned on table 6 which compares the seropositivity rate and median antibody titer values for both vaccines has 552 participants!