Report on mRNA-vaccination induced antibody responses measured with the Proel Biotech SARS-CoV-2 IgG detection kit (partial results)
Mónika Korodi, Gabriella Hudák, Zsuzsanna Jenei, István Horváth, Kinga Rákosi, and Szilard N. Fejer
Pro-Vitam Diagnostics and Research Centre & Proel Biotech Ltd.
16 Muncitorilor Street, Sfantu Gheorghe, Romania
Here we present the partial results of a study that aims to follow the kinetics of immune response due to vaccination with Comirnaty, an mRNA-based vaccine against COVID-19. The vaccine contains the genetic information necessary for synthesis of the SARS-CoV-2 spike protein. Immune response is directed against this protein, therefore IgG antibodies can be detected with diagnostic kits that contain the spike protein or its subunits (S1, S2, RBD). Our diagnostic kit contains as capture antigens the S1 domain of the spike protein and the nucleocapsid protein of SARS-CoV-2, therefore it can be simultaneously used for determining immune response due to COVID-19 and immune response due to vaccination.
The study follows the mounting immune response due to vaccination for more than 130 healthcare workers in four different Romanian cities. We have preliminary high-quality data on mounting immune response for 65 of the participants. Among these, 30 are already past day 7 after the second vaccine dose, and 26 participants are between 19-25 days post-vaccination.
Determination of SARS-CoV-2 IgG quantities was carried out according to the instructions of the Elisa kit. Samples were taken weekly from the participants (some patients donated samples more frequently), starting with the day of vaccination with the first dose. IgG quantities were determined in arbitrary units, as a signal to cutoff ratio. The cutoff was determined during product development in order to minimise false positives.
The results are summarized in Figure 1. Each patient is represented with a different symbol, lines connect the determined IgG values for the same patient. We observe two distinct antibody responses that depend on the previous exposure of the participant to SARS-CoV-2. Individuals that have been infected previously mount a quick immune response, irrespectively of the detected IgG quantity at the day of vaccination. Participants that tested negative for SARS-CoV-2 IgG antibodies at the day of vaccination and had large IgG quantities 7 days post-vaccination are all patients that were previously infected, as confirmed by RT-PCR.
For participants that had no previous exposure to the virus, the increase of IgG levels is gradual. 3 weeks post-vaccination, 44% of previously not infected participants are positive for SARS-CoV-2 IgG antibodies (signal to cutoff ratio >1 AU/ml), while 28-30 days post vaccination 97% of these participants are positive for these antibodies. Two participants tested below 1 AU/ml, in the inconclusive range (>0.9 AU/ml), one of those tested positive a day later, while we do not have follow-up result for the second participant yet. Among the cohort of previously infected individuals, 100% of the participants are positive for IgG antibodies 14 days after vaccination. The antibody quantities of the previously infected individuals are on average twice as high as for those that have only been vaccinated and not previously exposed to the virus, but it is expected that the levels of these two cohorts converge in a few weeks.
The Proel Biotech SARS-CoV-2 IgG Elisa kit was developed to detect only IgG antibodies with a high binding affinity to SARS-CoV-2 S1 and nucleocapsid antigens. Compared to other diagnostic kits on the market, our Elisa kit does not detect low to medium-binding SARS-CoV-2 IgG antibodies. The immune system produces antibodies of different qualities as a response to infection or vaccination, the antibody-producing cells mature over time and get selected for more efficient antibody production on subsequent antigenic exposure. Antibody-based protection is efficient only when the patient has tightly binding antibodies. We expect that the quantity of antibodies detected with the Proel Biotech Elisa kit as a response to vaccination correlates well with the quantity of neutralising antibodies, and therefore shows the level of protection of an individual. We plan long term follow-up for this cohort of healthcare workers (6-12 months) to assess the change in IgG quantity over time.
Change of SARS-CoV-2 IgG antibodies over time, starting from the day of vaccination. Note: the vertical scale is logarithmic, for better visibility of the change of IgG quantities in the cohort of participants that were not previously infected with SARS-CoV-2. The two cohorts have separate behaviour of antibody responses, as illustrated above (previously infected) and below (previously not infected) the red line.