SARS-CoV-2 IgG3 antibodies: friends or foe?

General: Antibodies (Ab) play an important role in the prevention and treatment of infectious diseases, including COVID-19. Effective antibodies against the pathogen, SARS-CoV2, were developed at unprecedented speed using biotechological methods. These are on the market as therapeutic agents. A disadvantage of this, however, is that they only work at the beginning of an infection and are also not particularly efficient. Improvements are required. One feature the approved SARS-CoV2 Abs have in common is that they are IgG1 subtypes. However, serum studies have shown that other subtypes, particularly IgG3, are induced after SARS-CoV2 infection. This points to an important role of IgG3 in virus control. However, the properties of these Ab subtype have been investigated very incompletely, since the production is particularly difficult. Research question/goal: The overarching goal of this largely biotechnologically oriented application is to produce, characterize and test the applicability of SARS-CoV-2 Abs of the IgG3 subtype for therapy. An innovative approach to the production of these unstable Ab variants is particularly important. Approach: A plant-based system will be used to produce SARS-CoV-2 IgG3 Abs. In the first step, highly stable IgG3 types are to be produced by systematically introducing small mutations. In a second step, the variants are then examined for their function, e.g. how efficiently they can neutralize SARS-CoV2 variants. In a final step, the laboratory results are monitored in an animal model. Result: Ideally, the results provide guidelines for a better design of SARS-CoV-2 Abs to be used in therapy and prevention. In addition, the results can provide information on the development of more efficient vaccines. Research Team: The program brings together research groups with complementary expertise, including Molecular Biotechnology, Ab-Engineering, Viral Biology and Immunology. This offers a major international competitive advantage and the results could serve as a template for treating other viral infections.