The impact of glycoyslation on filovirus vaccine immunogenicity in mice

Abstract

Abstract Filoviruses are highly virulent pathogens which cause severe hemorrhagic fevers, including Ebola virus disease (EVD). There is currently an ongoing large outbreak in the Democratic Republic of Congo, and while investigational vaccines have been used in trials during the outbreak, there are no licensed vaccines to EVD, or the related Marburg virus disease (MVD). The glycoproteins of filoviruses are the only virally expressed proteins on the virion surface and are required for receptor binding and as such, they are the main candidate vaccine antigen. A major component of the glycoprotein are the N- and O-linked glycans, but these glycans vary in number, distribution and type depending on the cell type producing the glycoprotein. Both mammalian and insect cell lines are commonly used to produce filovirus proteins used in vaccine development, but produce proteins with very different glycosylation. Here, we describe the impact of the filovirus glycoprotein glycans on the immunogenicity of the transmembrane-deleted glycoprotein (GPdTM) vaccine in mice using insect-produced, mammalian-produced, and deglycosylated filovirus glycoproteins. Results suggest differences in antibody titer and T cell epitopes induced between glycoproteins with different glycosylation patterns. Studies are underway to test how these changes affect survival against live virus challenge with mouse-adapted Ebola and Marburg.