Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates.

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Pascal KE, Dudgeon D, Trefry JC, Anantpadma M, Sakurai Y, Murin CD, Turner HL, Fairhurst J, Torres M, Rafique A, Yan Y, Badithe A, Yu K, Potocky T, Bixler SL, Chance TB, Pratt WD, Rossi FD, Shamblin JD, Wollen SE, Zelko JM, Carrion R Jr, Worwa G, Staples HM, Burakov D, Babb R, Chen G, Martin J, Huang TT, Erlandson K, Willis MS, Armstrong K, Dreier TM, Ward AB, Davey RA, Pitt MLM, Lipsich L, Mason P, Olson W, Stahl N, Kyratsous CA

Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates.

J Infect Dis. 2018 Nov 22;218(suppl_5):S612-S626. doi: 10.1093/infdis/jiy285.

PubMed ID

29860496 [ View in PubMed

]

Abstract

Background: For most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases. Methods: In this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses. Results: Of the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcgammaRIIIa. Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent. Conclusions: This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.

DrugBank Data that Cites this Article

Drugs

Atoltivimab

Maftivimab

Odesivimab

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Atoltivimab	Envelope glycoprotein	Protein	Zaire ebolavirus (strain Mayinga-76)	Yes	Antagonist	Details
Maftivimab	Envelope glycoprotein	Protein	Zaire ebolavirus (strain Mayinga-76)	Yes	Antagonist	Details
Odesivimab	Envelope glycoprotein	Protein	Zaire ebolavirus (strain Mayinga-76)	Yes	Antagonist	Details