title: Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice.
abstract: West Nile virus (WNV) is a mosquito-transmitted flavivirus and an emerging pathogen in many parts of the world. In the elderly and immunosuppressed, infection can progress rapidly to debilitating and sometimes fatal neuroinvasive disease. Currently, no WNV vaccine is approved for use in humans. As there have been several recent outbreaks in the United States and Europe, there is an increasing need for a human WNV vaccine. In this study, we formulated the ectodomain of a recombinant WNV envelope (E) protein with the particulate saponin-based adjuvant Matrix-M™ and studied the antigen-specific immune responses in mice. Animals immunized with Matrix-M™ formulated E protein developed higher serum IgG1 and IgG2a and neutralizing antibody titers at antigen doses ranging from 0.5 to 10 μg compared to those immunized with 3 or 10 μg of E alone, E adjuvanted with 1% Alum, or with the inactivated virion veterinary vaccine, Duvaxyn(®) WNV. This phenotype was accompanied by strong cellular recall responses as splenocytes from mice immunized with Matrix-M™ formulated vaccine produced high levels of Th1 and Th2 cytokines. Addition of Matrix-M™ prolonged the duration of the immune response, as elevated humoral and cellular responses were maintained for more than 200 days. Importantly, mice vaccinated with Matrix-M™ formulated E protein were protected from lethal challenge with both lineage 1 and 2 WNV strains. In summary, Matrix-M™ adjuvanted E protein elicited potent and durable immune responses that prevented lethal WNV infection, and thus is a promising vaccine candidate for humans.
authors.affiliation: Novavax AB, Uppsala, Sweden. Electronic address: smagnusson@novavax.com.
authors.forename: Sofia E
authors.initials: SE
authors.lastname: Magnusson
authors.affiliation: Novavax AB, Uppsala, Sweden.
authors.forename: Karin H
authors.initials: KH
authors.lastname: Karlsson
authors.affiliation: Novavax AB, Uppsala, Sweden.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Reimer
authors.affiliation: University of Zürich, Institute of Virology, Switzerland.
authors.forename: Silke
authors.initials: S
authors.lastname: Corbach-Söhle
authors.affiliation: University of Zürich, Institute of Virology, Switzerland.
authors.forename: Sameera
authors.initials: S
authors.lastname: Patel
authors.affiliation: Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St Louis, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Richner
authors.affiliation: Institute of Virology, University of Veterinary Medicine, Vienna, Austria; Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
authors.forename: Norbert
authors.initials: N
authors.lastname: Nowotny
authors.affiliation: Department of Molecular Medicine, University of Padova, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
authors.affiliation: Novavax AB, Uppsala, Sweden.
authors.forename: Karin Lövgren
authors.initials: KL
authors.lastname: Bengtsson
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ulbert
authors.affiliation: Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St Louis, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Novavax AB, Uppsala, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Stertman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014901:West Nile Fever / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000276:immunology*; D014902:West Nile virus / Q000145:classification*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins; D053060:West Nile Virus Vaccines
keywords: Adjuvant; Matrix M™; Vaccine; West Nile virus