Research Category: M2: Infectious Diseases

FY: 2005 Funding (in dollars): $100,000

Responsible Organization: U.S. ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES

Primary Contact: MRMC: U.S. Army Medical Research Institute of Infectious Diseases
City: Fort Detrick
State: MD
Zip: 21702-5011

Keywords: LABORATORY ANIMALS EBOLA

Objective:
The objective of this protocol is to develop NHP models for aerosol exposure to EBOV. The first step in this development is to use the staircase method to measure the response of NHP to infection by varying doses of aerosolized virus. The median lethal dose (LD for aerosolized ZEBOV will be determined in the cynomolgus macaque. Following determination of the LD5O, a small group of animals will be exposed to low and high lethal doses of ZEBOV in order to collect data concerning the disease course and clinical signs of ZEBOV infection, data which will be important for future vaccine efficacy studies Based on prior and ongoing studies with MARV and personal communicat10ns from Russian scientists, we hypothesize that the LD5O of aerosolized ZEBOV will be higher than what is thought to be the LOSO of ZEBOV by a parenteral route (? 1 pfu). These experiments will then be repeated with SEBOV. Finally, we will look at the outcome of aerosol exposure in rhesus macaques and African greens to compare and contrast differences in disease course and outcome with the cynomolgus macaque.

Approach:
Ebola viruses (EBOV) are highly infectious by aerosol and are considered a potential biological warfare threat against U.S. Armed Forces. In order to test candidate vaccines, animal models are needed for aerosol exposure to EBOV Nonhuman primates (NHP) are the closest animal models to humans, and the Reed,A05-02disease course and outcome of many diseases are similar be primates and humans. This protocol will begin the development of a NHP model of aerosol exposure to EBOV for use in vaccine efficacy studies. This protocol will determine the challenge dose to be used for future vaccine studies and examine clinical signs of exposure (fever, pulse, blood pressure changes in white blood cells, blood clothn9 and liver en to determine what if any signs can predict the outcome of infection. In addition, we will assess three different species of NHP in order to establish the most appropriate model of human exposure.
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Research was conducted in compliance with the Animal Welfare Act and other Federal statutes and regulations relating to the use of animals in research and was reviewed and approved by the Institute's Animal Care and Use Committee.