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A
nonhuman primate model of Rickettsia prowazekii infection Institution: Tulane University Health Sciences Center, Tulane National Primate Research Center, Covington, LA
Principal Investigator: Chad Roy, PhD
Expected Product:Development of a nonhuman primate model for epidemic typhus, using intravenous and aerosolized Rickettsia prowazekii.
Description: Rickettsia
prowazekii is the causative agent of epidemic typhus, a vector
(louse)-borne disease characterized by a sudden onset of febrile
symptoms with significant pathologic sequelae. In addition to
causing epidemic disease in poor and unhygienic environments,
R. prowazekii has also been identified as possessing the characteristics
of a biological weapon. There presently is no vaccine available
for protection against epidemic typhus, although development
of new products is currently underway. A fully characterized
primate model of disease is needed to determine immune response,
safety, and protective efficacy of vaccine products developed
to protect against R. prowazekii infection. The goal of this
project is to develop a robust nonhuman model of disease for
epidemic typhus in order to accelerate testing of newly developed
vaccine products. The specific hypothesis is that use of the
Rhesus macaque (Macaca mulatta) of Asian (Chinese) origin will
provide an optimal test system for an infection model of epidemic
typhus. We base this hypothesis upon the observations from limited
past studies that detailed 1) a clear dose-response relationship
in prior model development efforts with the Breinl strain using
Rhesus macaques when directly compared to experimental infection
with avirulent strains, and 2) typical pathology in the form
of disseminated vasculitis including typhus nodules in the central
nervous system that emulated the human clinical syndrome. Based
on these observations, the experimental focus of this proposal
is on the model development of epidemic typhus in the Rhesus
macaque. |
