title: Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine.
abstract: West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United States alone, no vaccine is available for use in humans. Here, we present a scaled manufacturing approach for production of a hydrogen peroxide-inactivated whole virion WNV vaccine, termed HydroVax-001WNV. Vaccination resulted in robust virus-specific neutralizing antibody responses and protection against WNV-associated mortality in mice or viremia in rhesus macaques (RM). A GLP-compliant toxicology study performed in rats demonstrated an excellent safety profile with clinical findings limited to minor and transient irritation at the injection site. An in vitro relative potency (IVRP) assay was developed and shown to correlate with in vivo responses following forced degradation studies. Long-term in vivo potency comparisons between the intended storage condition (2-8°C) and a thermally stressed condition (40±2°C) demonstrated no loss in vaccine efficacy or protective immunity over a 6-month span of time. Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001WNV is a promising vaccine candidate.
authors.affiliation: Najít Technologies, Inc, Beaverton, OR, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Poore
authors.affiliation: Najít Technologies, Inc, Beaverton, OR, USA.
authors.forename: Dawn K
authors.initials: DK
authors.lastname: Slifka
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Beaverton, OR, USA.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Raué
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Beaverton, OR, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Beaverton, OR, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Hammarlund
authors.affiliation: Najít Technologies, Inc, Beaverton, OR, USA.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Quintel
authors.affiliation: Najít Technologies, Inc, Beaverton, OR, USA.
authors.forename: Lindsay L
authors.initials: LL
authors.lastname: Torrey
authors.affiliation: Najít Technologies, Inc, Beaverton, OR, USA.
authors.forename: Ariel M
authors.initials: AM
authors.lastname: Slifka
authors.affiliation: Departments of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Richner
authors.affiliation: Najít Technologies, Inc, Beaverton, OR, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Dubois
authors.affiliation: BioFinity Consulting, Beaverton, OR, USA.
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Johnson
authors.affiliation: Departments of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Najít Technologies, Inc, Beaverton, OR, USA; Division of Neuroscience, Oregon National Primate Research Center, Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Beaverton, OR, USA.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Slifka
authors.affiliation: Najít Technologies, Inc, Beaverton, OR, USA. Electronic address: iamanna@najittech.com.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Amanna
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008807:Mice, Inbred BALB C; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D014481:United States; D064166:Vaccine Potency; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000302:isolation & purification; D014766:Viremia / Q000517:prevention & control; D014901:West Nile Fever / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000891:Anti-Infective Agents, Local; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D053060:West Nile Virus Vaccines; D006861:Hydrogen Peroxide
keywords: Antibody; Hydrogen peroxide; Rhesus macaque; Vaccination; Vaccine; West Nile virus