title: Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice.
abstract: Ebola virus is a Filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. Filoviruses are classified as "Category A bioterrorism agents", and currently there are no licensed therapeutics or vaccines to treat and prevent infection. The Filovirus glycoprotein (GP) is sufficient to protect individuals against infection, and several vaccines based on GP are under development including recombinant adenovirus, parainfluenza virus, Venezuelan equine encephalitis virus, vesicular stomatitis virus (VSV) and virus-like particles. Here we describe the development of a GP Fc fusion protein as a vaccine candidate. We expressed the extracellular domain of the Zaire Ebola virus (ZEBOV) GP fused to the Fc fragment of human IgG1 (ZEBOVGP-Fc) in mammalian cells and showed that GP undergoes the complex furin cleavage and processing observed in the native membrane-bound GP. Mice immunized with ZEBOVGP-Fc developed T-cell immunity against ZEBOV GP and neutralizing antibodies against replication-competent VSV-G deleted recombinant VSV containing ZEBOV GP. The ZEBOVGP-Fc vaccinated mice were protected against challenge with a lethal dose of ZEBOV. These results show that vaccination with the ZEBOVGP-Fc fusion protein alone without the need of a viral vector or assembly into virus-like particles is sufficient to induce protective immunity against ZEBOV in mice. Our data suggested that Filovirus GP Fc fusion proteins could be developed as a simple, safe, efficacious, and cost effective vaccine against Filovirus infection for human use.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Konduru
authors.forename: Steven B
authors.initials: SB
authors.lastname: Bradfute
authors.forename: Jerome
authors.initials: J
authors.lastname: Jacques
authors.forename: Mohanraj
authors.initials: M
authors.lastname: Manangeeswaran
authors.forename: Siham
authors.initials: S
authors.lastname: Nakamura
authors.forename: Sufi
authors.initials: S
authors.lastname: Morshed
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wood
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.forename: Gerardo G
authors.initials: GG
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D046129:Ebola Vaccines / Q000276:immunology*; D029043:Ebolavirus / Q000276:immunology; D057809:HEK293 Cells; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D056724:Immunity, Humoral; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D010948:Viral Plaque Assay
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D046129:Ebola Vaccines; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus