Translational research related to Corona-Covid 19 (COVID-19)

The unpredictability of the COVID-19 disease course poses a major burden on health care and economic systems across the world. This is mainly caused by a lack of in-depth knowledge of the diverse host factors that dictate COVID-19’s severity. While it is known that the immune response to SARS-CoV-2 can become heavily dysregulated leading to patients’ admissions to intensive care units, the details of how and when this happens remain largely elusive. This lack of knowledge also poses major threats to ongoing interventional clinical trials, which, even though they are focused at the administration of immunomodulatory therapeutics, remain largely blinded with respect to patient selection and timing of administration (e.g. too early or too late). Apart from some disease factors (age, co-morbidity, gender) of which the pathophysiological mechanism is unknown, very little knowledge exists.

To date, several antiviral compounds and vaccines are under development. In addition, passive immunization with anti-SARS-CoV-2 neutralizing IgG antibodies obtained from plasma provided by COVID-19 convalescent patients is being studied as a therapeutic option for patients infected with SARS-CoV-2 and for patients at high risk for harmful evolution. However, the disadvantage is that it relies on a complex logistic process, i.e. collection of plasma, testing for neutralizing antibodies and inactivation from possible pathogens. Therefore, a more interesting strategy is to use recombinant anti-SARS-CoV-2 monoclonal antibodies that can be identified from convalescent patients and produced in vitro. Of note, monoclonal antibody treatment has yielded promising results as anti-Ebola virus therapy.

In this project, we aim to profile the antibody response of COVID-19 patients with different disease severities. We are uniquely positioned to perform such studies because of our validated mass spectrometry (MS) based work-flow to identify disease-related antibody peptides and unique microfluidic-based platform to isolate and individually interrogate and clone the B cell receptor (i.e. the monoclonal antibody) from single B cells of patients. The impact is directed to fill the gap(s) to further understand the disease course and inter-individual differences. The immediate outcome will be the identification of prognostic serological antibody-related biomarkers to guide therapeutic strategies and the identification and characterization of a (protective) human monoclonal antibody panel. The project results will also directly contribute to improve the insight in disease mechanisms for steering vaccine/drug development.

More in particular, we aim to reach the following specific research objectives:

• Objective 1: CDR profiling of sera from COVID-19 patients and identification of the specific antibody sequences that react with the SARS-CoV-2 antigens
• Objective 2: Isolate and characterize a panel of fully human monoclonal antibodies sourced from convalescent patients with high levels of neutralizing antibodies that can be used for (or contribute to) further drug development.