Making Universal Vaccines and Antibodies Through Glycoengineering.

Abstract

Biological glycosylation is a process used by nature to modulate the structure and function of biomolecules, particularly the glycoproteins on the surface of cells. Most human viruses, for example, depend on the host glycosylation machinery to create a sugar coat on the viral surface to facilitate infection and escape immune surveillance. The main immunogens of influenza and COVID viruses are mostly shielded by the sugar coat from immune response, so deletion of the sugar coat would expose the highly conserved epitopes and elicit broadly protective antibody and T cell responses against the virus and different variants. In addition to increased memory T cell response, the antibodies induced by such low-sugar vaccines are more diverse with higher titers against the immunogen, especially the highly conserved epitopes, thus broadening the scope of protection. Furthermore, the Fc-glycans on the antibody can be engineered to improve antibody-mediated killing. This review highlights the impact of glycosylation engineering on the development of universal vaccines and antibodies with improved Fc-mediated killing.