title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.
abstract: Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab')2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab')2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Xuexing
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Hualei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Shihua
authors.initials: S
authors.lastname: He
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Changchun Institute of Biological Products Co. Ltd., Changchun, China.
authors.forename: Weijin
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Jin
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gai
authors.affiliation: Changchun Institute of Biological Products Co. Ltd., Changchun, China.
authors.forename: Di
authors.initials: D
authors.lastname: Chu
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Zengguo
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center for Disease Control and Prevention, Chengdu Military Region, Kunming, China.
authors.forename: Quanshui
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Chi
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Feihu
authors.initials: F
authors.lastname: Yan
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Huang
authors.affiliation: Center for Disease Control and Prevention, Chengdu Military Region, Kunming, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Yuetao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Changchun Institute of Biological Products Co. Ltd., Changchun, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.|Department of Medical Microbiology, Winnipeg, Manitoba, Canada.|Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.|Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: George Fu
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.|Department of Medical Microbiology, Winnipeg, Manitoba, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Yang
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage*; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology*; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D006736:Horses; D007128:Immunoglobulin Fragments / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000914:Antibodies, Viral; D007128:Immunoglobulin Fragments; D007155:Immunologic Factors