Research Article
Evaluation of Different Strategies for Post-Exposure Treatment of Ebola Virus Infection in Rodents
Jason S. Richardson1#, Gary Wong1,3#, Stéphane Pillet1, Samantha Schindle1, Jane Ennis2, Jeffrey Turner2, James E. Strong1,3 and Gary P. Kobinger1,3,4*
1Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
2Defyrus Incorporated, Toronto, Ontario, Canada
3Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
4Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
#The authors contributed equally to the work.
- *Corresponding Author:
- Gary P. Kobinger, PhD
Special Pathogens Program
National Microbiology Laboratory
Public Health Agency of Canada
1015 Arlington Street,Winnipeg
MB, R3E 3R2, Canada
Tel: 204-784-5923
Fax: 204-789-2140
E-mail: gary_kobinger@phac-aspc.gc.ca
Received Date: August 31, 2011; Accepted Date: October 18, 2011; Published Date: October 20, 2011
Citation: Richardson JS, Wong G, Pillet S, Schindle S, Ennis J, et al. (2011) Evaluation of Different Strategies for Post-Exposure Treatment of Ebola Virus Infection in Rodents. J Bioterr Biodef S1:007. doi: 10.4172/2157-2526.S1-007
Copyright: © 2011 Richardson JS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Zaire Ebola virus (ZEBOV) is a pathogen that causes severe hemorrhagic fever in humans and non-human
primates. There are currently no licensed vaccines or approved treatments available against ZEBOV infections. The goal of this work was to evaluate different treatment strategies in conjunction with a replication deficient, recombinant human adenovirus serotype 5 (Ad-CAGopt)-based vaccine expressing the Zaire Ebola virus glycoprotein (ZGP) in Ebola infected mice and guinea pigs. Guinea pigs were treated with Ad-CAGoptZGP in combination with different treatment strategies after challenge with guinea pig adapted-ZEBOV (GA-ZEBOV). B10.BR mice were used to further characterize efficacy and immune
responses following co-administration of Ad-CAGoptZGP with the most effective treatment: AdHu5 expressing recombinant IFN-α (hereafter termed DEF201) after challenge with a lethal dose of mouse adapted-ZEBOV (MA-ZEBOV). In mice, DEF201 treatment was able to elicit full protection against a lethal dose of MA-ZEBOV when administered 30 minutes after infection. In guinea pigs the Ad-CAGoptZGP and DEF201 combination therapy elicited full protection when treated 30 minutes post-exposure and were a superior treatment to Ad-CAGoptZGP supplemented with recombinant IFN-α protein. Further analysis of the immune response revealed that addition of DEF201 to Ad-CAGoptZGP enhances the resulting adaptive immune response against ZGP. The results highlight the importance of the innate immune response in the prevention of ZEBOV pathogenesis and support further development of the Ad-CAGoptZGP with DEF201 treatment combination for post-exposure therapy against ZEBOV infection.
