Broad antibody-based protection against SARS-CoV-2 through Fc-mediated opsonization

Monoclonal antibodies have been widely used as a therapy for COVID-19 with neutralizing antibodies that block viral invasion. However, virus mutations of such neutralizing epitopes have made these monoclonals obsolete.

Still, a typical immune response mostly leads to antibodies that instead help clear the infection by promoting immune cell function through Fc-mediated opsonization. The constant antibody domain determines its class and subclass and directly influences immune effects via their Fc.

We have recently shown that opsonizing antibodies can protect against SARS-CoV-2 independent of their neutralizing capability and that switching subclass can improve the immune response against the virus.

Further, this antibody-mediated immune function can be enhanced by combining antibodies into cocktails.In this project, we will develop broadly binding protective antibodies by targeting conserved epitopes of the viral S and M proteins. By leveraging Fc-mediated mechanisms, many more epitopes are available, increasing the chances of success.

These antibodies will be enhanced through antibody engineering by exploring class-switching and the creation of hybrid antibodies.

Besides potential new broadly-binding therapeutic antibodies against SARS-CoV-2, the project will also lead to new general insights into how antibody subclass engineering and incorporating antibodies into cocktails can modulate the efficacy of antibodies as potential therapeutics against viral infections.