title: Recombinant proteins of Zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice.
abstract: Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death. Questions remain with regard to the few survivors of infection, who manage to mount an effective adaptive immune response. These questions concern the humoral and cellular components of this response, and whether such a response can be elicited by an appropriate prophylactic vaccine. The data reported herein describe the production and evaluation of a recombinant subunit Ebola virus vaccine candidate consisting of insect cell expressed Zaire ebolavirus (EBOV) surface glycoprotein (GP) and the matrix proteins VP24 and VP40. The recombinant subunit proteins are shown to be highly immunogenic in mice, yielding both humoral and cellular responses, as well as highly efficacious, providing up to 100% protection against a lethal challenge with live virus. These results demonstrate proof of concept for such a recombinant non-replicating vaccine candidate in the mouse model of EBOV which helps to elucidate immune correlates of protection and warrants further development.
authors.affiliation: PanThera Biopharma, LLC, Aiea, HI 96701, United States. Electronic address: lehrer@hawaii.edu.
authors.forename: Axel T
authors.initials: AT
authors.lastname: Lehrer
authors.affiliation: PanThera Biopharma, LLC, Aiea, HI 96701, United States.
authors.forename: Teri-Ann S
authors.initials: TS
authors.lastname: Wong
authors.affiliation: Hawaii Biotech, Inc., Aiea, HI 96701, United States.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lieberman
authors.affiliation: Hawaii Biotech, Inc., Aiea, HI 96701, United States.
authors.forename: Tom
authors.initials: T
authors.lastname: Humphreys
authors.affiliation: Hawaii Biotech, Inc., Aiea, HI 96701, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Clements
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, United States.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Bakken
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, United States.
authors.forename: Mary Kate
authors.initials: MK
authors.lastname: Hart
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, United States.
authors.forename: William D
authors.initials: WD
authors.lastname: Pratt
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD 21702, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Dye
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D046129:Ebola Vaccines / Q000276:immunology*; D029043:Ebolavirus; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D046129:Ebola Vaccines; C446938:VP24 protein, Ebola virus; C080981:VP40 protein, virus; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins
keywords: GP; Recombinant subunit proteins; Subunit vaccine; VP24; VP40; Zaire ebolavirus