Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 213, Issue 7, Pages 1124-1133Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv565
Keywords
Ebola; therapeutic; neutralization; antibody; efficacy
Categories
Funding
- Wellcome Trust
- MicroPharm
- PHE Pipeline Fund
- Medical Research Council [MR/L009528/1]
- Wellcome Trust [090532/Z/09/Z]
- Medical Research Council [MR/L009528/1] Funding Source: researchfish
- MRC [MR/L009528/1] Funding Source: UKRI
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The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP(1,2)) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP(1,2ecto)) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease.
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