Throughout history, pandemics like the Black Death or the Spanish Flue have periodically wiped out large parts of populations.Today, history repeats itself with the on-going SARSCoV-2 pandemic, which manifests that pandemics still hold the potential to cause devastating impact to global health and economy.To prevent severe illness and death, epidemics have been fought with polyclonal antibodies derived from immunized animals, since this technol. was invented by Behring and Kitasato in 1890 [1].Since then, major advances have occurred in the field of immunotherapy, enabled particularly by the advent of recombinant DNA technol. and a range of discovery methodologies that allow for the generation and manufacture of (human) monoclonal antibodies and antibody fragments [2].These advances strengthen our ability to react to infectious diseases with pandemic potential and have already been put to utility in a number of cases [3].As an example, during the 2014-2016 Ebola outbreak in West Africa, a mixture of three monoclonal antibodies (ZMappTM) originating from two prior antibody mixtures (MB003 and Zmab) were combined and rapidly used for treatment of Ebola infected patients despite lacking prior clin. trials to prove safety and efficacy [4].The antibody mixture was shown to be beneficial to the patients, although it did not reach statistical significance compared to standard of care [5].In addition, therapeutic monoclonal antibodies have been, or are currently being developed for H1N1 [6], SARS, MERS [7], and SARS-CoV-2 [8].While vaccine development is supreme to reduce mortality in a pandemic situation, and convalescent plasma or small mols. sometimes can be used for treatment, an urgent need also exists for fast development of therapeutic monoclonal antibodies as a complement.These antibodies can be administered to groups responding weakly to vaccination, such as immunocompromised patients, or prophylactically as a first line of defense for people at high risk of being infected and/ or becoming severely ill.In addition, if prompt testing to detect infected people is in place, an opportunity may exist to administer antibodies as a precaution and treatment before clin. manifestations occur, thereby possibly reducing the severity of an infection.

2021-12-01·Genome medicine1区 · 生物学

Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care

1区 · 生物学

ArticleOA

作者: Rickett, Natasha Y ; Ng, Lisa F P ; Fletcher, Tom ; García-Dorival, Isabel ; Jacobs, Michael ; Bosworth, Andrew ; Thomson, Emma C ; Matthews, David A ; Carroll, Miles W ; Dong, Xiaofeng ; Hiscox, Julian A

Abstract:

Background:

Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013–2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient—perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD.

Methods:

Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood.

Results:

The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a ‘fatal’ outcome to a ‘survival’ outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence—such as defective interfering genomes.

Conclusions:

The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.

2017-03-01·Immunotherapy4区 · 医学

The Ongoing Evolution of Antibody-Based Treatments for Ebola virus Infection

4区 · 医学

Review

作者: Mendoza, Emelissa J ; Kobinger, Gary P ; Racine, Trina

The 2014–2016 Ebola virus outbreak in West Africa was the deadliest in history, prompting the evaluation of various drug candidates, including antibody-based therapeutics for the treatment of Ebola hemorrhagic fever (EHF). Prior to 2014, only convalescent blood products from EHF survivors had been administered to newly infected individuals as a form of treatment. However, during the recent outbreak, monoclonal antibody cocktails such as ZMapp, ZMAb and MB-003 were either tested in a human clinical safety and efficacy trial or provided to some based on compassionate grounds. This review aims to discuss the evolution of antibody-based treatments for EHF, their clinical trial efficacy and the development of new antibody-based therapies currently advancing in preclinical testing.

100 项与 ZMAb (Defyrus, Inc.) 相关的药物交易

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