Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody

Corti, Davide; Misasi, John; Mulangu, Sabue; Stanley, Daphne A.; Kanekiyo, Masaru; Wollen, Suzanne E.; Ploquin, Aurélie; Doria‐Rose, Nicole A.; Staupe, Ryan P.; Bailey, Michael; Shi, Wei; Choe, Misook; Marcus, Hadar; Thompson, Emily A.; Cagigi, Alberto; Silacci, Chiara; Fernandez-Rodriguez, Blanca; Perez, Laurent; Sallusto, Federica; Vanzetta, Fabrizia; Agatic, Gloria; Cameroni, Elisabetta; Kisalu, Neville K.; Gordon, Ingelise J.; Ledgerwood, Julie E.; Mascola, John R.; Graham, Barney S.; Muyembe-Tamfun, Jean-Jacques; Trefry, John C.; Lanzavecchia, Antonio; Sullivan, Nancy J.

doi:10.1126/science.aad5224

Cited by 389 publications

(418 citation statements)

References 23 publications

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“…MAb114 has in vitro activity against recent and previous outbreak variants of Ebola and monotherapy with mAb114 fully protected three rhesus macaques when given as late as 5 days after a challenge with a lethal dose of EBOV [31]. This study suggests that a single antibody has therapeutic potential.…”

Section: Mab114mentioning

confidence: 65%

“…The individual mAbs each binds to one of three distinct regions; the GP base (where GP1 and GP2 interface), a glycan cap, or a mucin-like domain (Figure 2). MAbs binding to the GP base (4G7 and 2G4) are neutralizing in vitro, whereas antibodies binding the glycan caps (mAb114, 1H3, and 13C6) or the mucin-like domains (13F6 and 6D8) appear non-neutralizing in vitro [13], with the exception of mAb114 [31]. 13C6 and 6D8 do neutralize in presence of complement [32].…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…MAb114 is a human monoclonal antibody, recently isolated from a survivor of the 1995 EVD outbreak in the Democratic Republic of Congo [31]. MB-003 and ZMAb are monoclonal antibody cocktails isolated from immunized mice.…”

Section: Introduction Of the Compoundsmentioning

confidence: 99%

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Monoclonal antibodies for the treatment of Ebola virus disease

Moekotte

Huson

Ende³

et al. 2016

Expert Opinion on Investigational Drugs

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Introduction: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMapp ™ and MIL-77E cocktails.Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.ARTICLE HISTORY

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Section: Mab114mentioning

confidence: 65%

Section: Pharmacodynamicsmentioning

confidence: 99%

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Monoclonal antibodies for the treatment of Ebola virus disease

Moekotte

Huson

Ende³

et al. 2016

Expert Opinion on Investigational Drugs

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“…In addition to ZMapp, other groups have recently explored the use of human anti-EBOV GP mAbs as treatments in NHPs. Specifically, Corti et al 145 showed that mono therapy with mAb114 completely protected rhesus monkeys from 1,000 PFU EBOV (Kikwit strain) challenge at 50 mg per kg beginning either 1 day (three of three; treatment regimen on days 1, 2 and 3) or 5 days (three of three; treatment regimen on days 5, 6 and 7) 145 after EBOV exposure.…”

mentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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“…These retentive antibodies in Ebola survivors can be used as effective therapeutic against Ebola. The successful outcome of the animal model that derived monoclonal antibodies in nonhuman primates reflects the importance of monoclonal antibodies against Ebola [4].…”

Section: Survivor's Blood -An Alternative Approachmentioning

confidence: 99%