IGIB: In vaccinated people, Covishield first dose is highly immunogenic if already infected

In a small study involving just 135 health-care workers who were vaccinated with Covishield, IGIB researchers found that antibody levels are significantly higher in those already infected prior to the first dose of vaccination compared with virus-naïve individuals. At day 14, antibodies were detectable in health-care workers who were not infected prior to vaccination, and the levels increased further on day 28.

A small study involving just 135 health-care workers who were vaccinated with Covishield at a tertiary hospital in Delhi estimated the effectiveness of the vaccine after the first dose in terms of antibody levels. It found that the antibody levels following vaccination were much higher in those who were already infected than in those who were not.

The results have been posted on medRxiv preprint server. Preprints are yet to be peer-reviewed and published in scientific journals.

Though measurements were made only till day 28 after the first dose, there is a clear indication that the antibody levels are significantly higher in those already infected prior to the first dose of vaccination compared with virus-naïve individuals. Further studies to measure the antibody levels 15 days after the second dose may help provide evidence that policy makers can use for delaying the second dose of Covishield vaccine.

Currently in India, people who receive the Covishield vaccine are required to take the second dose 28 days after the first. Based on phase-3 trial data that showed delaying the second dose to 8-12 weeks after the first increased the vaccine efficacy, the British regulator had approved delaying the second dose.

How the study was conducted

Of the 135 people studied, 44 (32.5%) health-care workers were found to be already infected with SARS-CoV-2 virus even before being vaccinated with the first dose. All the 44 people had already developed antibodies to the virus prior to vaccination. The team from the Delhi-based Institute of Genomics and Integrative Biology (CSIR-IGIB) which undertook the study assigned all the 135 individuals to two groups based on the presence/absence of antibodies prior to the first dose of vaccination.

The levels of antibodies were tested at four time points — day 0, 7, 14 and 28. Of these 135 people studied, the blood samples were collected from 53 people at all four time points and the antibody levels measured. Samples were collected from all 135 people on day 28.

Highly immunogenic in infected people

“On day seven after the first dose, the antibody levels were very high in people who were already infected, while those who were not infected prior to vaccination almost did not show any antibodies on day seven,” says Dr. Shantanu Sengupta from IGIB and one of the corresponding authors of the preprint. “At day 14, antibodies were detectable in health-care workers who were not infected prior to vaccination, and the levels increased further on day 28.”

“Even on day 28, compared with those who were not infected prior to vaccination, the antibody levels are significantly higher in people who were already infected,” Dr. Sengupta adds. “The antibody levels clearly show an increasing trend in people uninfected before vaccination. How much more it would increase after day 28 needs to be studied.”

The median antibody levels in 44 people who were already infected were 66.5 units per millilitre (U/mL) on day zero, which then increased to 5,857 units per millilitre on day 28. In comparison, the median antibody levels in 91 individuals who were not already infected prior to vaccination reached just 0.4 on day seven and 32.1 units per millilitre on day 28.

Immunogenicity in infected and virus-naïve people

In the subset of 53 individuals whose antibody levels were measured at all four time points, the median antibody levels in 14 individuals who were already infected were 153 units per millilitre on day zero, which further increased to 4,413.5 units per millilitre on day seven. It increased further to 10,560.5 and 13,180 units per millilitre on day 14 and 28, respectively.

In comparison, the median antibody levels in 39 individuals who were not already infected prior to vaccination reached just 0.4 units per millilitre on day seven, 2.1 and 26 units per millilitre on day 14 and 28, respectively.

“Our data suggests that the Oxford vaccine is highly immunogenic, particularly so where previous SARS CoV2 antibody-response is established. Given the high background seropositivity in India, this may be useful in determining optimal timing of the second dose during mass immunisation within the constraints of vaccine supply and administration,” they write.

The researchers also write: “Our data supports safely delaying the second dose in recipient groups with high sero-positivity. This could be adopted as a universal strategy, given that the first dose seems to give adequate protection lasting for about three months in other studies, or could be one part of a dual strategy where high-risk or vulnerable populations receive the second dose earlier, while normal-risk subjects have a delayed second dose.”