Pathologies arising through epidemic spreads of life-threatening pathogens are becoming an increasing threat of global societies and their social systems. Among those are to mention the current SARS CoV2-virus derived pandemic, the worldwide raising multi-drug resistant bacteria (MDR) or other infectious threats with poor or missing treatment options.
VERAXA has implemented superior screening procedures to rapidly indentify neutralizing anti-viral antibodies out of immune cells from convalescent patients or from immunized murine organisms. The neutralizing function of antibodies can be assessed in one single screening step based on special phenotypic cell-based assays in a microfluidic format. As the neutralizing functions of antibodies are not necessarily correlated to their antigen-binding strength, the conventional two step methodology most probably will not shuffle all the rare and therapeutically relevant hits.
Moreover, a binding-biased pre-selection of antibodies may result in a phenomenon called Antibody Dependent Enhancement (ADE), characterized by viral infections of primary immune cells with unclear and unwanted possible implications for future therapeutics use.
In a typical setting, the viral particles used in the screen can transduce the host cell with a fluorescent function after viral invasion. In that case, only droplets containing non-fluorescent reporter cells will be sorted out and the encapsulated B-cells will be recovered and sequenced for the expressed mAb. Alternative systems can be used including virus silencing reporter gene expression in the host cell in which case positive hits are being selected.
Anti-bacterial antibodies can be screened by co-encapsulating fluorescently labeled bacteria in droplets together with antibody-secreting B-cells. Any antibody, that binds to the bacteria and either inhibits their growth or kills them will cause a relative reduction in the fluorescence level as compared to that of normally growing bacteria (intensity and spatial concentration).
For better mimicking of in vivo conditions, additional components of the immune system such as complement can be added to the droplets to assay antibody-mediated complement activity (AMCA). These droplets are then sorted out and the encapsulated B-cells furthermore analyzed.