Immunotherapeutics for Ebola Virus Disease: Hope on the Horizon

O’Donnell, Kyle L.; Marzi, Andrea

doi:10.2147/btt.s259069

Cited by 9 publications

(5 citation statements)

References 58 publications

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“…MB-003 (human or human-mouse chimeric mAbs c13C6, h13F6, and c6D82) is amongst the most potent and effective combinations [ 27 ]. Another cocktail is ZMapp, composed of m1H3, m2G4, and m4G7 murine mAbs, expedited for clinical trials during the 2013–2016 EBOV pandemic in West Africa, with encouraging preclinical evidence [ 28 , 29 ]. Interestingly, ZMapp—a mixture of three mAbs that are not protective if administered individually—was shown to protect non-human primates from a fatal EBOV challenge [ 29 , 30 ].…”

Section: Progress In Developing Antiviral Mabsmentioning

confidence: 99%

Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections

et al. 2022

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Monoclonal antibodies (mAbs), the new revolutionary class of medications, are fast becoming tools against various diseases thanks to a unique structure and function that allow them to bind highly specific targets or receptors. These specialized proteins can be produced in large quantities via the hybridoma technique introduced in 1975 or by means of modern technologies. Additional methods have been developed to generate mAbs with new biological properties such as humanized, chimeric, or murine. The inclusion of mAbs in therapeutic regimens is a major medical advance and will hopefully lead to significant improvements in infectious disease management. Since the first therapeutic mAb, muromonab-CD3, was approved by the U.S. Food and Drug Administration (FDA) in 1986, the list of approved mAbs and their clinical indications and applications have been proliferating. New technologies have been developed to modify the structure of mAbs, thereby increasing efficacy and improving delivery routes. Gene delivery technologies, such as non-viral synthetic plasmid DNA and messenger RNA vectors (DMabs or mRNA-encoded mAbs), built to express tailored mAb genes, might help overcome some of the challenges of mAb therapy, including production restrictions, cold-chain storage, transportation requirements, and expensive manufacturing and distribution processes. This paper reviews some of the recent developments in mAb discovery against viral infections and illustrates how mAbs can help to combat viral diseases and outbreaks.

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Section: Progress In Developing Antiviral Mabsmentioning

confidence: 99%

Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections

et al. 2022

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“…Entry of EBOV is mediated by several cell surface attachement factors and the intracellular receptor Niemann-Pick C1 (NPC1) with no dependence on ACE2 [22]. Treatment of cells with Type I IFNs renders cells resistant against EBOV infection [23] and has been shown to be beneficial for extended survival in infected nonhuman primates and Ebola virus disease patients [24,25]. EC cultures were left untreated or treated with IFNα or β for the indicated times and infected with EBOV at an MOI of 5.…”

Section: Interferon Alpha or Beta Induced Ace2 But Not Delta Ace2 In Pulmonary Endothelial Cellsmentioning

confidence: 99%

Interferon-alpha or -beta facilitates SARS-CoV-2 pulmonary vascular infection by inducing ACE2

et al. 2021

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Severe viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a hyperinflammatory state typified by elevated circulating pro-inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection and subsequent endothelial damage have been described in patients with fatal COVID-19, the mechanism by which this occurs remains elusive, particularly given that, under naïve conditions, pulmonary endothelial cells demonstrate minimal cell surface expression of the SARS-CoV-2 binding receptor ACE2. Herein we describe SARS-CoV-2 infection of the pulmonary endothelium in postmortem lung samples from individuals who died of COVID-19, demonstrating both heterogeneous ACE2 expression and endothelial damage. In primary endothelial cell cultures, we show that SARS-CoV-2 infection is dependent on the induction of ACE2 protein expression and that this process is facilitated by type 1 interferon-alpha (IFNα) or -beta(β)—two of the main anti-viral cytokines induced in severe SARS-CoV-2 infection—but not significantly by other cytokines (including interleukin 6 and interferon γ/λ). Our findings suggest that the stereotypical anti-viral interferon response may paradoxically facilitate the propagation of COVID-19 from the respiratory epithelium to the vasculature, raising concerns regarding the use of exogenous IFNα/β in the treatment of patients with COVID-19.

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“…The genus Ebolavirus belongs to the Filoviridae family and includes six species: Bombali ebolavirus, Bundibugyo ebolavirus, Reston ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus, and Zaire ebolavirus 11 . The EBOV are viruses that contain linear, non-segmented, negative-sense, single-stranded genomic RNA 12 .…”

Section: Introductionmentioning

confidence: 99%

Designing a novel multi‑epitope vaccine against Ebola virus using reverse vaccinology approach

Alizadeh

Amini‐Khoei

Tahmasebian

et al. 2022

Sci Rep

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Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings.

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Immunotherapeutics for Ebola Virus Disease: Hope on the Horizon

Cited by 9 publications

References 58 publications

Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections

Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections

Interferon-alpha or -beta facilitates SARS-CoV-2 pulmonary vascular infection by inducing ACE2

Designing a novel multi‑epitope vaccine against Ebola virus using reverse vaccinology approach

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