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From: TSS ()
Subject: Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route
Date: September 29, 2007 at 12:50 pm PST

P04.27

Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route


Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3;
Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1
1Paul-Ehrlich-Institut, Germany; 2Commissariat ŕ l´Energie Atomique, France; 3Instituto
Superiore di Sanitŕ, Italy; 4Swedish Institute for Infectious Disease control, Sweden;
5Georg August University, Germany; 6German Primate Center, Germany


Background:

In 2001, a study was initiated in primates to assess the risk for humans
to contract BSE through contaminated food. For this purpose, BSE brain was
titrated in cynomolgus monkeys.


Aims:

The primary objective is the determination of the minimal infectious dose (MID50)
for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for
humans. Secondly, we aimed at examining the course of the disease to identify
possible biomarkers.


Methods:


Groups with six monkeys each were orally dosed with lowering amounts of
BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study,
animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).


Results:


In an ongoing study, a considerable number of high-dosed macaques already
developed simian vCJD upon oral or intracerebral exposure or are at the onset of the
clinical phase. However, there are differences in the clinical course between orally and
intracerebrally infected animals that may influence the detection of biomarkers.


Conclusions:


Simian vCJD can be easily triggered in cynomolgus monkeys on the oral
route using less than 5 g BSE brain homogenate. The difference in the incubation
period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However,
there are rapid progressors among orally dosed monkeys that develop simian vCJD as
fast as intracerebrally inoculated animals.


The work referenced was performed in partial fulfilment of the study “BSE in primates“
supported by the EU (QLK1-2002-01096).


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


TSS



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