Abstract
Ebola virus (EBOV), a member of the family Filoviridae, is responsible for causing Ebola virus disease (EVD) (formerly named Ebola hemorrhagic fever). This is a severe, often fatal illness with mortality rates varying from 50 to 90% in humans. Although the virus and associated disease has been recognized since 1976, it was only when the recent outbreak of EBOV in 2014–2016 highlighted the danger and global impact of this virus, necessitating the need for coming up with the effective vaccines and drugs to counter its pandemic threat. Albeit no commercial vaccine is available so far against EBOV, a few vaccine candidates are under evaluation and clinical trials to assess their prophylactic efficacy. These include recombinant viral vector (recombinant vesicular stomatitis virus vector, chimpanzee adenovirus type 3-vector, and modified vaccinia Ankara virus), Ebola virus-like particles, virus-like replicon particles, DNA, and plant-based vaccines. Due to improvement in the field of genomics and proteomics, epitope-targeted vaccines have gained top priority. Correspondingly, several therapies have also been developed, including immunoglobulins against specific viral structures small cell-penetrating antibody fragments that target intracellular EBOV proteins. Small interfering RNAs and oligomer-mediated inhibition have also been verified for EVD treatment. Other treatment options include viral entry inhibitors, transfusion of convalescent blood/serum, neutralizing antibodies, and gene expression inhibitors. Repurposed drugs, which have proven safety profiles, can be adapted after high-throughput screening for efficacy and potency for EVD treatment. Herbal and other natural products are also being explored for EVD treatment. Further studies to better understand the pathogenesis and antigenic structures of the virus can help in developing an effective vaccine and identifying appropriate antiviral targets. This review presents the recent advances in designing and developing vaccines, drugs, and therapies to counter the EBOV threat.
Highlights
Ebola virus (EBOV; Zaire ebolavirus) is the causative agent of a severe hemorrhagic fever disease, Ebola virus disease (EVD; formerly called Ebola hemorrhagic fever)
The present review aims to discuss advances in designing and development of EBOV vaccines, drugs, antibody-based treatments, and therapeutics, and their clinical efficacy in limiting EVD, thereby providing protection against the disease and alleviating high public health concerns associated with EBOV
EBOV filamentous virus-like particle (VLP) were observed in the supernatant of cells resulting from co-expression of GP and VP40 and post immunization, specific humoral accompanied with a mixed Th1/Th2 cellular immune response was obtained
Summary
Ebola virus (EBOV; Zaire ebolavirus) is the causative agent of a severe hemorrhagic fever disease, Ebola virus disease (EVD; formerly called Ebola hemorrhagic fever). An EBOV vaccine capable of effectively inducing a long-lasting neutralizing antibody response is desirable for developing appropriate prevention strategies in combating the infection In this line, the mucin-like domain of EBOV envelope glycoprotein GP1 has been identified to be critical in induction of protective humoral immune response [46, 47]. Efficacy trials initiated to test the rVSV-vectored EBOV vaccine showed greater efficiency at the time of EVD outbreak, if deployed following the strategy of ring vaccination [80] Another recombinant vaccine (VSV based), i.e., rVSV-Zaire EBOV has been shown to provide substantial protection. Ebola vaccine potency trials employing replication defective adenoviral vectors (rAd) encoding EBOV GP have come up with promising results in NHP models Based on such studies, multiple mutant glycoproteins were developed (such as glycoprotein with deleted transmembrane domain) which offers reduced in vitro cytopathogenicity but possessed reduced vaccine-mediated protection. Similar results were obtained by Hensley et al [140], with no significant antiviral
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