Projects Infectious Disease Epidemiology
Based on the importance of antibody responses as a benchmark for SARS-CoV-2 immunity, we have developed in cooperation with the Natural and Medical Sciences Institute at the University of Tübingen (NMI). MULTICOV-AB, a multiplex serology test which is used to measure endemic and pandemic coronavirus antibody responses. The established test system provides detailed information on the antibodies against different SARS-CoV-2 antigens as well as against antigens of all endemic, “common cold” coronaviruses (OC43, NL63, 229E and HKU1) in blood and saliva samples. The assay generates high-resolution data to assess at population level, the prevalence of SARS-CoV-2 compared to other respiratory viruses, as well as the duration of SARS-CoV-2 protective immune response and SARS-CoV-2 susceptibility of individuals to infection. One advantage of the multiplex-based Luminex technology is its high flexibility which is well-illustrated by the rapid and constant expansion of the MULTICOV-AB antigen panel with the antigens of emerging SARS-CoV-2 isolates such as the alpha, beta, gamma, delta or omicron variants. Thus, MULTICOV-AB contributes to the analysis of pre-existing SARS-CoV-2 antibody responses and their efficiency in preventing infections with emerging variants.
Differentiation of infection- and vaccine-induced immune responses is possible, for example, due to distinct pathogen structures in vaccine and wild-type strains or by using inactivated vaccines, which only lead to antibody formation against certain pathogen components. The latter principle was used a basis for a serology assay to differentiate immune responses following hepatitis A virus infection from those of a vaccination by determining if HAV2A-specific antibodies are present in a sample. In cooperation with Joop van den Heuvel (HZI) and Ulrich Kalinke (TWINCORE), the potential of three structurally distinct Hepatitis B virus (HBV) antigens to serve as vaccination or infection biomarkers will be investigated. To establish this differential HBV immunoassay, the selected antigens a virus-like particle, the HBsAg surface protein -representing the vaccine, alone and an inactive HBV particle will be evaluated using a well-characterized sera sample set. Last, this synthetic biology approach will also be tested to determine if retrospective genotyping of hepatitis B infections based on the genotype-specific amino acid sequences of the hepatitis B surface proteins using a multiplex approach is possible.
While we are developing and evaluating products that allow participants of epidemiological cohort studies to self-sample at home, we are equally interested in establishing techniques that simplify post-collection specimen storage. These self-sampling techniques are less invasive, less expensive, and easier to use and to transport than for instance conventional blood sampling by venipuncture. The development of those self-sampling and storage methods from the first idea to proof of concept, is done in collaboration with experts from various scientific and engineering disciplines.
Differential Serology for SARS-CoV-2
Comparative magnitude and persistence of humoral SARS-CoV-2 vaccination responses on a population level in Germany.
A. Dulovic, B. Kessel, M. Harries, M. Becker, J. Ortmann, J. Griesbaum, J. Jüngling, D. Junker, P. Hernandez, D. Gornyk, S. Glöckner, V. Melhorn, S. Castell, J.K. Heise, Y. Kemmling, T. Tonn, K. Frank, T. Illig, N. Klopp, N. Warikoo, A. Rath, C. Suckel, A.U. Marzian, N. Grupe, P.D. Kaiser, B. Traenkle, U. Rothbauer, T. Kerrinnes, G. Krause, B. Lange§, N. Schneiderhan-Marra, M. Strengert:
Frontiers In Immunology (2022).
Diminishing immune responses against variants of concern in dialysis patients four months after SARS-CoV-2 mRNA vaccination.
A. Dulovic, M. Strengert, G. M. Ramos, M. Becke, D. Junker, J. Griessbaum, K. Lürken, A. Beigel, E. Wrenger, G. Lonnemann, A. Cossmann, M. V. Stankov, A. Dopfer-Jablonka, P. D. Kaiser, B. Traenkle, U. Rothbauer, G. Krause, N. Schneiderhan-Marra, G. M. N. Behrens;
Emerg Infect Dis. 2022 Apr;28(4):743-750. doi: 10.3201/eid2804.211907.
Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis.
M. Strengert*, M. Becker*, G. M. Ramos*, A. Dulovic, J. Gruber, J. Jüngling, K. Lürken, A. Beigel, E. Wrenger, G. Lonnemann, A. Cossmann, M. V. Stankov, A. Dopfer-Jablonka, P. D. Kaiser, B. Traenkle, U. Rothbauer, G. Krause, N. Schneiderhan-Marra, G. M. N. Behrens
Lancet eBiomedicine (2021).
Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity.
Becker M.*, Strengert M.*, Junker D., Kaiser P., Kerrinnes T., Traenkle B., Dinter H., Häring J., Ghozzi S., Zeck A., Weise F., Peter A., Hörber S., Fink S., Ruoff F., Dulovic A., Bakchoul T., Baillot A., Lohse S., Cornberg M., Illig T., Gottlieb J., Smola S., Karch A., Berger K., Rammensee H., Schenke-Layland K., Nelde A., Märklin M., Heitmann J., Walz J., Templin M., Joos T., Rothbauer U., Krause G., Schneiderhan-Marra N.
Nature Communications (2021).
Differenzielle serology for hepatitis viruses
Validation of HAV biomarker 2A for differential diagnostic of hepatitis A infected and vaccinated individuals using multiplex serology.
Katrin Bohm, Angela Filomena, Nicole Schneiderhan-Marra, Gérard Krause, Claudia Sievers,
Vaccine, Volume 35, Issue 43, 2017, doi.org/10.1016/j.vaccine.2017.08.089.
Recombinant Transient Gene Expression and Preparation of HBsAg VLPs for Serology and Structural Analysis.
M. Lehky, M. Strengert, N. Scheinderhan-Marra, T. Kerrinnes, M. Müsken, J. van den Heuvel
Instruct Biennial Structural Biology Conference Changes in structural biology: challenges in studying dynamics. Utrecht, May 2022.