Deglycosylated Filovirus Glycoproteins as Effective Vaccine Immunogens
Abstract
Viruses within the two filoviral genera, Ebolavirus (EBOV) and Marburgvirus (MARV), continue to cause episodic outbreaks in Africa. In addition, because these viruses can be aerosolized, there is concern that these viruses will be weaponized, leading to the listing of filoviruses on the CDC and NIAID select agents Category A biodefense pathogens list. No antivirals or vaccines against these deadly hemorrhagic viruses are currently available, although a number of experimental vaccines have proven successful against homologous challenge in rodents and nonhuman primates. All vaccines that are being tested include in their composition the heavily glycosylated filovirus glycoprotein (GP) that is sufficient for protection against homologous lethal challenge. Evidence indicates that protection is primarily mediated by antibodies (Abs) raised against the GP that can neutralize the homologous antigen, but have little to no neutralizing capabilities against GPs from other filovirus species. The current challenge in the field is to develop an EBOV vaccine that not only protects against challenge with the homologous virus, but is also protective against other filoviruses and no univalent immunogen currently provides such broad efficacy. Studies with other enveloped viruses demonstrate that deglycosylation of the viral glycoprotein yields an immunogen that provides better protection against lethal challenge with the homologous strain of virus and yields enhanced antibody binding of more distantly related viruses. In this application, we propose to determine if removal of glycans on EBOV GP will expose cryptic epitopes within conserved regions of the glycoprotein, thereby enhancing the production of antibodies that will protect against homologous and heterologous challenge. With strong preliminary data supporting this work, we propose to assess the protection afforded by our glycan mutant GPs against EBOV and MARV challenge.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2015
- Accession Number
- AD1030126
Entities
People
- Wendy Maury
Organizations
- University of Iowa