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Out of Nowhere
Published in Rae-Ellen W. Kavey, Allison B. Kavey, Viral Pandemics, 2020
Rae-Ellen W. Kavey, Allison B. Kavey
In selected cases, infected Westerners and healthcare workers have been given antiviral agents like ZMapp, a combination of three antiviral antibodies, and plasma transfusions from individuals who had recovered from Ebola and both measures seemed to possibly improve outcomes if given early in the course of the illness. There is ongoing investigation of several different therapeutic strategies that target specific viral structures and mechanisms of Ebola viruses, some of which have demonstrated promising results in animal studies. These include agents composed of interfering RNAs targeting specific proteins of Ebola viruses, hyperimmune globulin isolated from Ebola animal models, monoclonal antibodies, and morpholino oligomers, small molecules used to block viral gene expression. Limited reports indicate that simple provision of intravenous fluids and oxygen significantly improves patient outcomes.133 The goals of therapeutic agents include prevention of disease development after exposure and moderation of EVD severity and duration.134
Considerations and Bayesian Applications in Pharmaceutical Development for Rare Diseases
Published in Mani Lakshminarayanan, Fanni Natanegara, Bayesian Applications in Pharmaceutical Development, 2019
Bayesian statistics naturally and systematically borrowing strength from previously collected data. However, it has been slowly adopted into registry clinical programs due to clinical and statistical inertia. Through the last two case examples, we have seen the potential of using Bayesian statistics to maximize the information at hand and simplify simulation process for trial design. Because of Ebola virus disease (EVD) outbreak in West Africa 2014–2016,51,52a much needed more efficient adaptive trial design was used in the investigation of a new drug ZMapp developed by Mapp Biopharmaceutical.53
African Cities and Ebola
Published in Igor Vojnovic, Amber L. Pearson, Gershim Asiki, Geoffrey DeVerteuil, Adriana Allen, Handbook of Global Urban Health, 2019
Zacchaeus Anywaine, Ggayi Abubaker Mustapher
Small molecule drugs have shown potential in treating EVD in pre-clinical studies, including Favipiravir, a pyrazinecarboxamide derivative currently used in the treatment of influenza virus. Other drugs worthy of consideration include lamivudine, TKM-Ebola, Ribavirin and Brincidofovir. Monoclonal antibodies (MAbs) known as ZMapp have also been developed. ZMapp is an improved IgG MAb cocktail comprising MAbs from two precursors, ZMAb (providing MAbs c2G4 and c4G7) and MB-003 (providing MAb c13C6). This was found to be efficacious in NHPs and used in the two American patients during the 2014–2016 Ebola epidemic with promising results.
Reproducibility and flexibility of monoclonal antibody production with Nicotiana benthamiana
Published in mAbs, 2022
Kelsi Swope, Josh Morton, Gregory P. Pogue, Leigh Burden, Nicholas Partain, Steve Hume, John Shepherd, Carrie A. Simpson, Miles B. Brennan, Thomas C. Furman, Sheila Kingrey-Gebe, Theresa Martinez, Jim McDonough, Michael H. Pauly, Kevin J. Whaley, Larry Zeitlin, Barry Bratcher, Hugh Haydon
The production of the three mAbs evaluated in Phase 1/2 clinical trials for treatment of Ebola virus infection provides an example of the speed with which this platform can be deployed (Figure 5). The initial case for the 2014–2016 Ebola outbreak occurred in December 2013 and a medical alert was issued in January 2014 for the region in Guinea where multiple cases occurred.17 Within one month of identifying the potentially therapeutic antibodies, small quantities of the three antibodies were produced for a pilot study in non-human primates. Based on the positive outcome of that study,18 in August of the same year, GMP production was initiated, and a few patients received the mAb cocktail, named ZMapp, through expanded access/compassionate use.19 By October of 2014, ZMapp was available, and the investigational new drug (IND) application was approved in February 2015, enabling initiation of the clinical trials.
Review of Ebola virus disease in children – how far have we come?
Published in Paediatrics and International Child Health, 2021
Devika Dixit, Kasereka Masumbuko Claude, Lindsey Kjaldgaard, Michael T. Hawkes
ZMapp. ZMapp is a cocktail of monoclonal antibodies directed against the Zaire Ebola virus glycoprotein (GP) [87]. Pre-clinical efficacy was demonstrated in a non-human primate model of EBV [88]. It is administered intravenously in three doses on days 0, 3 and 6 of hospitalisation. Between 2014 and 2015, eight patients in the USA and Europe received ZMapp, alone or in combination with other EVD therapeutics [62]. Subsequently, a clinical trial, Partnership for Research on Ebola Virus in Liberia (PREVAIL) II, was conducted, randomising 72 patients to ZMapp or standard care (1:1 ratio, 36 per group) in Liberia, Sierra Leone, Guinea and the USA [87]. Fifteen children under 18 years of age received ZMapp in the study [87]. Although mortality appeared to be lower in the ZMapp group, the difference did not reach a pre-defined statistical threshold for efficacy [87]. In the PALM study, ZMapp was given to 169 EVD patients, including 20 children <5 years of age and 14 aged 5–18 years [68]. Mortality in the ZMapp group was 84/169 (50%) and was used as the comparator group for other experimental agents [68]. Fever and hypotension with ZMapp infusion have been reported, which can be managed by slowing the infusion or using antipyretic agents [87]. Fever, hypotension, agitation, tachycardia, tachypnoea, flushing, palmar pruritus and rash were reported in adult EVD patients receiving ZMapp in the USA and Europe [62].
Will plant-made biopharmaceuticals play a role in the fight against COVID-19?
Published in Expert Opinion on Biological Therapy, 2020
Today, plant-made biopharmaceuticals have become a reality. At least one product has entered the market, namely taliglucerase alfa, a carrot-made enzyme obtained in bioreactors that is prescribed as replacement therapy for Gaucher´s disease [10]. Other products are close to be approved, for instance, clinical trials are ongoing to evaluate influenza vaccines produced by Medicago Inc [13]. Moreover, Zmapp (a plant-made monoclonal antibody cocktail) was placed in the spotlight during the Ebola outbreak in 2014 since it was administered to two patients on a compassionate basis to treat a few patients [14]. Although other antibodies have shown better performance, this plant-made antibody cocktail has revealed the potential of the technology in the fight against emerging diseases [15]. Today glycoengineering approaches are available to yield specific antibody glycoforms, which will allow optimizing the functional activity and safety of the target antibodies [16]. Moreover, functional single chain antibodies are also produced in plant systems; providing simpler molecules for viral neutralization [17]. Plant-made antigens and antibodies can be also convenient tools for diagnosis; providing low-cost proteins with preserved antigenic determinants and specificity [18,19].