Long-Term Humoral Immune Response against SARS-CoV-2 after Natural Infection and Subsequent Vaccination According to WHO International Binding Antibody Units (BAU/mL)
Natalia Ruetalo,
Bertram Flehmig,
Michael Schindler,
Lutz Pridzun,
Angelika Haage,
Marija Reichenbächer,
Thomas Kirchner,
Teresa Kirchner,
Karin Klingel,
Michael B. Ranke,
Andrea Normann
Affiliations
Natalia Ruetalo
Institute for Medical Virology and Epidemiology, University Hospital Tuebingen, Elfriede-Aulhorn-Str. 6, 72076 Tuebingen, Germany
Bertram Flehmig
Paediatric Endocrinology, University Children’s Hospital, Hoppe-Seyler-Str. 1, 72076 Tuebingen, Germany
Michael Schindler
Institute for Medical Virology and Epidemiology, University Hospital Tuebingen, Elfriede-Aulhorn-Str. 6, 72076 Tuebingen, Germany
Lutz Pridzun
Mediagnost Gesellschaft für Forschung und Herstellung von Diagnostika GmbH, Aspenhaustr. 25, 72770 Reutlingen, Germany
Angelika Haage
Mediagnost Gesellschaft für Forschung und Herstellung von Diagnostika GmbH, Aspenhaustr. 25, 72770 Reutlingen, Germany
Marija Reichenbächer
Mediagnost Gesellschaft für Forschung und Herstellung von Diagnostika GmbH, Aspenhaustr. 25, 72770 Reutlingen, Germany
Thomas Kirchner
Pediatric Practice, Kapuzinerberg 17, 71263 Weil der Stadt, Germany
Teresa Kirchner
Pediatric Practice, Kapuzinerberg 17, 71263 Weil der Stadt, Germany
Karin Klingel
Institute for Pathology and Neuropathology, University Hospital Tuebingen, Liebermeisterstr. 8, 72076 Tuebingen, Germany
Michael B. Ranke
Paediatric Endocrinology, University Children’s Hospital, Hoppe-Seyler-Str. 1, 72076 Tuebingen, Germany
Andrea Normann
Mediagnost Gesellschaft für Forschung und Herstellung von Diagnostika GmbH, Aspenhaustr. 25, 72770 Reutlingen, Germany
The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralization activity were evaluated in three patients after a mild course of COVID-19. Serum samples were collected frequently during a period of over one year. Furthermore, in two individuals, the effects of an additional vaccination with a mRNA vaccine containing the S1-RBD sequence on these antibodies were examined. After natural infection, the antibodies (IgA, IgG) against the S1-protein remained elevated above the established cut-off to positivity (S-IgA 60 BAU/mL and S-IgG 50 BAU/mL, respectively) for over a year in all patients, while this was not the case for ABs against the N-protein (cut-off N-IgG 40 BAU/mL, N-IgA 256 BAU/mL). Sera from all patients retained the ability to neutralize SARS-CoV-2 for more than a year. Vaccination resulted in a rapid boost of antibodies to S1-protein but, as expected, not to the N-protein. Most likely, the wide use of the WHO reference preparation will be very useful in determining the individual immune status of patients after an infection with SARS-CoV-2 or after vaccination.
