Abstract
Hemorrhagic fever viruses are among the deadliest pathogens known to humans, and often, licensed medical countermeasures are unavailable to prevent or treat infections. Guinea pigs are a commonly used animal for the preclinical development of any experimental candidates, typically to confirm data generated in mice and as a way to validate and support further testing in nonhuman primates. In this chapter, we use Sudan virus (SUDV), a lethal filovirus closely related to Ebola virus, as an example of the steps required for generating a guinea pig-adapted isolate that is used to test a monoclonal antibody-based therapy against viral hemorrhagic fevers.
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References
Falzarano D, Feldmann H (2013) Vaccines for viral hemorrhagic fevers—progress and shortcomings. Curr Opin Virol 3(3):343–351. doi:10.1016/j.coviro.2013.04.007
CDC.gov (2013) Viral Hemorrhagic Fevers. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/vhf.htm. Accessed March 31 2016
Safronetz D, Rosenke K, Westover JB, Martellaro C, Okumura A, Furuta Y, Geisbert J, Saturday G, Komeno T, Geisbert TW, Feldmann H, Gowen BB (2015) The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset. Sci Rep 5:14775. doi:10.1038/srep14775
McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM, Elliott LH, Belmont-Williams R (1986) Lassa fever. Effective therapy with ribavirin. N Engl J Med 314(1):20–26. doi:10.1056/NEJM198601023140104
Huggins JW, Hsiang CM, Cosgriff TM, Guang MY, Smith JI, Wu ZO, LeDuc JW, Zheng ZM, Meegan JM, Wang QN et al (1991) Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome. J Infect Dis 164(6):1119–1127
Kelley B (2009) Industrialization of mAb production technology: the bioprocessing industry at a crossroads. MAbs 1(5):443–452
Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP (2014) Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514(7520):47–53. doi:10.1038/nature13777
Lyon GM, Mehta AK, Varkey JB, Brantly K, Plyler L, McElroy AK, Kraft CS, Towner JS, Spiropoulou C, Stroher U, Uyeki TM, Ribner BS (2014) Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med 371(25):2402–2409. doi:10.1056/NEJMoa1409838
Bray M, Davis K, Geisbert T, Schmaljohn C, Huggins J (1998) A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever. J Infect Dis 178(3):651–661
Connolly BM, Steele KE, Davis KJ, Geisbert TW, Kell WM, Jaax NK, Jahrling PB (1999) Pathogenesis of experimental Ebola virus infection in guinea pigs. J Infect Dis 179(Suppl 1):S203–S217. doi:10.1086/514305
Qiu X, Alimonti JB, Melito PL, Fernando L, Stroher U, Jones SM (2011) Characterization of Zaire ebolavirus glycoprotein-specific monoclonal antibodies. Clin Immunol 141(2):218–227. doi:10.1016/j.clim.2011.08.008
Zeitlin L, Pettitt J, Scully C, Bohorova N, Kim D, Pauly M, Hiatt A, Ngo L, Steinkellner H, Whaley KJ, Olinger GG (2011) Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant. Proc Natl Acad Sci U S A 108(51):20690–20694. doi:10.1073/pnas.1108360108
CDC.gov (2016) Outbreaks chronology: Ebola virus disease. http://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html. Accessed March 31 2016
Wong G, He S, Wei H, Kroeker A, Audet J, Leung A, Cutts T, Graham J, Kobasa D, Embury-Hyatt C, Kobinger GP, Qiu X (2015) Development and characterization of a guinea pig-adapted Sudan Virus. J Virol 90(1):392–399. doi:10.1128/JVI.02331-15
Howell KA, Qiu X, Brannan JM, Bryn C, Davidson E, Holtsberg FW, Wec AZ, Shulenin S, Biggins JE, Douglas R, Turner HL, Pallesen J, Murin CD, He S, Kroeker A, Vu H, Herbert AS, Fusco ML, Nyakature EK, Lai JR, Saphire EO, Zeitlin L, Ward AB, Chandran K, Doranz BJ, Kobinger GP, Dye JM, Aman MJ (2016) Antibody treatment of Ebola and Sudan virus infection via a uniquely exposed epitope within the glycoprotein receptor-binding site. Cell Rep 15(7):1514–1526
Acknowledgments
G.W. is supported by the Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (CIHR) and the President’s International Fellowship Initiative from the Chinese Academy of Sciences (CAS).
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Wong, G., Bi, Y., Kobinger, G., Gao, G.F., Qiu, X. (2018). Testing Experimental Therapies in a Guinea Pig Model for Hemorrhagic Fever. In: Salvato, M. (eds) Hemorrhagic Fever Viruses. Methods in Molecular Biology, vol 1604. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6981-4_21
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DOI: https://doi.org/10.1007/978-1-4939-6981-4_21
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