West Nile Virus (WNV) represents a significant threat to public health in the United States, particularly in vulnerable populations such as the elderly and the immunocompromised. This mosquito-borne pathogen has spread throughout North America to countries including Canada and Mexico as well as to Central America, South America, and the Caribbean. Although most WNV infections are either mild or asymptomatic, neuroinvasive disease is accompanied by a high mortality rate (up to 35% in the hospitalized elderly). Moreover, up to 77% of survivors who recover from acute WNV encephalitis endure long-term neurological sequelae resulting in problems such as impaired gait, muscle weakness, hearing loss, and tremors for more than or equal to 3 years after infection. WNV is an emerging infectious disease and is listed as an NIAID Category B Priority Pathogen. Although there is an effective veterinary vaccine against WNV, there are currently no FDA-approved vaccines available for preventing human WNV infection. In this proposal, we will use a proprietary new platform technology for developing an inactivated vaccine formulation that can be used to immunize a diverse population including immunologically vulnerable groups such as the elderly. Our preliminary studies demonstrate that this vaccine approach is feasible, highly immunogenic (eliciting CD8+ T cell and neutralizing antibody responses) and protects mice against lethal WNV infection. In this project, we will evaluate candidate vaccine formulations in two animal models, perform scale-up development and cGMP manufacturing of the lead candidate vaccine, and perform benchmark preclinical studies necessary for preparing an IND application and initiating future Phase I clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI082196-04
Application #
8238380
Study Section
Special Emphasis Panel (ZAI1-BLG-M (J3))
Program Officer
Repik, Patricia M
Project Start
2009-04-15
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$1,097,443
Indirect Cost
$306,132
Name
Oregon Health and Science University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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Freeman, Bailey E; Meyer, Christine; Slifka, Mark K (2014) Anti-inflammatory cytokines directly inhibit innate but not adaptive CD8+ T cell functions. J Virol 88:7474-84
Pinto, Amelia K; Richner, Justin M; Poore, Elizabeth A et al. (2013) A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal West Nile virus infection in aged mice. J Virol 87:1926-36
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