We will develop and fully characterize an African green monkey model of Nipah virus (NiV) infection and we will use this model to evaluate existing and discover new therapeutic modalities for treating NiV infection. This proposal addresses the mission of the RCE program by focusing on critical research gaps identified by NIAID including: 1) basic biology of less well-studied NIAID Category A-C agents; 2) mechanisms of pathogenesis, with emphasis on less well-studied agents; 3) target identification for therapeutics;and 4) development of new animal models for pathogenesis studies and therapeutics evaluation. In addition, the proposal seeks to employ a broad-spectrum approach to treat a major feature of henipavirus infection (acute respiratory distress syndrome [ARDS]) in order to improve outcome. As ARDS is a prominent feature of other emerging infectious diseases this approach may have utility beyond henipaviruses.
SPECIFIC AIMS. In Aim 1, we will establish virus infection, lethal dose, and detection parameters of NiV in an African green monkey model.
In Aim 2, we will determine the protective efficacy of the existing drug ribavirin against NiV in the African green monkey.
In Aim 3, we will determine the passive protective efficacy of neutralizing, anti-G, fully-human monoclonal antibody therapy for NiV infection in the African green monkey.
In Aim 4, we will determine the mechanism of ARDS seen in NiV infections and evaluate the ability of broadspectrum anticoagulants to ameliorate the deleterious consequences of ARDS.
Nipah virus (NiV) is included among the select agents of biodefense concern and is presently classified as a priority pathogen in category C by the CDC and the NIAID. There are presently no approved active or passive therapeutic modalities for NiV infection resulting from a natural outbreak, laboratory accident, or deliberate misuse. This project seeks new treatments for NiV infection.
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