scholarly journals Passive Transfer of Antibodies Protects Immunocompetent and Immunodeficient Mice against Lethal Ebola Virus Infection without Complete Inhibition of Viral Replication

2001 ◽  
Vol 75 (10) ◽  
pp. 4649-4654 ◽  
Author(s):  
Manisha Gupta ◽  
Siddhartha Mahanty ◽  
Mike Bray ◽  
Rafi Ahmed ◽  
Pierre E. Rollin

ABSTRACT Ebola hemorrhagic fever is a severe, usually fatal illness caused by Ebola virus, a member of the filovirus family. The use of nonhomologous immune serum in animal studies and blood from survivors in two anecdotal reports of Ebola hemorrhagic fever in humans has shown promise, but the efficacy of these treatments has not been demonstrated definitively. We have evaluated the protective efficacy of polyclonal immune serum in a mouse model of Ebola virus infection. Our results demonstrate that mice infected subcutaneously with live Ebola virus survive infection and generate high levels of anti-Ebola virus immunoglobulin G (IgG). Passive transfer of immune serum from these mice before challenge protected upto 100% of naive mice against lethal Ebola virus infection. Protection correlated with the level of anti-Ebola virus IgG titers, and passive treatment with high-titer antiserum was associated with a delay in the peak of viral replication. Transfer of immune serum to SCID mice resulted in 100% survival after lethal challenge with Ebola virus, indicating that antibodies alone can protect from lethal disease. Thus antibodies suppress or delay viral growth, provide protection against lethal Ebola virus infection, and may not require participation of other immune components for protection.

Fractals ◽  
2021 ◽  
Author(s):  
SHAHER MOMANI ◽  
R. P. CHAUHAN ◽  
SUNIL KUMAR ◽  
SAMIR HADID

The Ebola virus infection (EVI), generally known as Ebola hemorrhagic fever, is a major health concern. The occasional outbreaks of virus occur primarily in certain parts of Africa. Many researches have been devoted to the study of the Ebola virus disease. In this paper, we have taken susceptible-infected-recovered-deceased-environment (SIRDP) system to investigate the dynamics of Ebola virus infection. We adopted fractional operators for a better illustration of model dynamics and memory effects. Initially, the Ebola disease model is modified with Caputo–Fabrizio arbitrary operator in Caputo sense (CFC) and we employed the fixed-point results for the existence and uniqueness of the solution of the fractional system. Further, we adopted the arbitrary fractional conformable and [Formula: see text]-conformable derivatives to the alternative representation of the model. For the numerical approximation of the system, we show a numerical technique based on the fundamental theorem of fractional calculus for CFC derivative and a numerical scheme called the Adams–Moulton for conformable derivatives. Finally, for the validation of theoretical results, the numerical simulations are displayed.


2003 ◽  
Vol 77 (2) ◽  
pp. 1069-1074 ◽  
Author(s):  
Ayato Takada ◽  
Heinz Feldmann ◽  
Ute Stroeher ◽  
Mike Bray ◽  
Shinji Watanabe ◽  
...  

ABSTRACT Ebola virus causes lethal hemorrhagic fever in humans, but currently there are no effective vaccines or antiviral compounds for this infectious disease. Passive transfer of monoclonal antibodies (MAbs) protects mice from lethal Ebola virus infection (J. A. Wilson, M. Hevey, R. Bakken, S. Guest, M. Bray, A. L. Schmaljohn, and M. K. Hart, Science 287:1664-1666, 2000). However, the epitopes responsible for neutralization have been only partially characterized because some of the MAbs do not recognize the short synthetic peptides used for epitope mapping. To identify the amino acids recognized by neutralizing and protective antibodies, we generated a recombinant vesicular stomatitis virus (VSV) containing the Ebola virus glycoprotein-encoding gene instead of the VSV G protein-encoding gene and used it to select escape variants by growing it in the presence of a MAb (133/3.16 or 226/8.1) that neutralizes the infectivity of the virus. All three variants selected by MAb 133/3.16 contained a single amino acid substitution at amino acid position 549 in the GP2 subunit. By contrast, MAb 226/8.1 selected three different variants containing substitutions at positions 134, 194, and 199 in the GP1 subunit, suggesting that this antibody recognized a conformational epitope. Passive transfer of each of these MAbs completely protected mice from a lethal Ebola virus infection. These data indicate that neutralizing antibody cocktails for passive prophylaxis and therapy of Ebola hemorrhagic fever can reduce the possibility of the emergence of antigenic variants in infected individuals.


Vaccine ◽  
2007 ◽  
Vol 25 (6) ◽  
pp. 993-999 ◽  
Author(s):  
Ayato Takada ◽  
Hideki Ebihara ◽  
Steven Jones ◽  
Heinz Feldmann ◽  
Yoshihiro Kawaoka

2021 ◽  
Author(s):  
Cheng Cao ◽  
Lin Zhu ◽  
Ting Gao ◽  
Xuan Liu

Abstract Ebola virus (EBOV), one of the deadliest viruses, is the cause of fatal Ebola hemorrhagic fever (EHF)1,2. The underlying mechanism of viral replication and EBOV-related hemorrhage is not fully understood. Here, we show that EBOV VP35, a cofactor of viral RNA-dependent RNA polymerase, binds human A kinase interacting protein (AKIP1), which consequently activates protein kinase A (PKA) and PKA-downstream transcription factor CREB1. During EBOV infection, CREB1 is recruited into EBOV ribonucleoprotein complexes in viral inclusion bodies (VIBs) and employed for viral replication. AKIP1 depletion or PKA-CREB1 inhibition dramatically impairs EBOV replication. Meanwhile, the transcription of several coagulation-related genes, including THBD and SERPINB2, is substantially upregulated by VP35-dependent CREB1 activation, which may contribute to EBOV-related hemorrhage. The finding that EBOV VP35 hijacks the host PKA-CREB1 signal axis for viral replication and pathogenesis provides novel potential therapeutic approaches against Ebola virus disease.


Author(s):  
Henny Elfira Yanti ◽  
Aryati Aryati

Ebola virus disease has known as Ebola hemorrhagic fever (EHF) is an acute viral syndrome characterized by fever and bleeding witha high mortality rate in humans and non human (primates). The current outbreak inWestern Africa is the largest ebola outbreak since theebola virus was first discovered in 1976. The first EHF case that reemerged back in Africa occurred in March 2014 and in Desember 29th2014 had been revealed 20,153 cases and 7,883 deaths. The virus is transmitted from wild animals and spread in the human populationthrough human –to -human transmission. Ebola virus infection is characterized by immunosuppression and systemic inflammatoryresponse. Both condition cause the damage of blood vessels, coagulation and disorders of the immune system, leading to multiple organfailure and shock. Until now there are no ebola standards treatment guidelines. However, the life survival increased with early supportivecare such as rehydration and symptomatic treatment.


Author(s):  
Michael B. A. Oldstone

This chapter examines the Ebola virus in detail. Since 1976, with the exception of the 2013–2016 epidemic in West Africa, all outbreaks of Ebola virus infection have occurred in central Africa. The initial 1976 eruption of Ebola in Zaire in central Africa provided lessons for how to control future outbreaks of this disease. Unfortunately, those lessons were not well learned or sufficiently applied to the massive Ebola outbreak that followed in 2013–2016 in western Africa. Ebola virus can spread either through the air or by exposure to contaminated blood of infected humans. The clinical course of Ebola virus infection is that of a severe hemorrhagic fever. An Ebola vaccine was developed and administered to over 40,000 individuals for the 2018–2019 outbreak. However, the vaccine’s effectiveness in the outbreak has not been formally assessed, and critical scientific assessment will be difficult to achieve. Ultimately, Ebola virus remains endemic in Africa. Whether the fruit bat is the only natural reservoir for such viruses, how Ebola is transmitted, and where it lurks are still unresolved.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhi-Yong Pan ◽  
Yan-Jun Wu ◽  
Ye-Xian Zeng ◽  
Hao Lin ◽  
Tian-Ao Xie ◽  
...  

Background. West Africa has witnessed the unprecedented outbreak of Ebola virus disease (EVD). The Ebola virus (EBOV) can cause Ebola hemorrhagic fever, which is documented as the most deadly viral hemorrhagic fever in the world. RT-PCR had been suggested to be employed in the detection of Ebola virus; however, this method has high requirements for laboratory equipment and takes a long time to determine Ebola infection. Although Xpert Ebola is a fast and simple instrument for the detection of Ebola virus, its effect is still unclear. This study is aimed at evaluating the accuracy of Xpert Ebola in diagnosing Ebola virus infection. Methods. Using the keywords “Xpert” and “Ebola virus”, relevant studies were retrieved from the database of PubMed, Embase, Web of Science, and Cochrane. RT-PCR was employed as a reference standard to evaluate whether the study is eligible to be included in the meta-analysis. Data from these included studies were extracted by two independent assessors and were then analyzed by the Meta-DiSc 1.4 software to produce the heterogeneity of sensitivity (SEN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) of the study. The results of pooled analysis were plotted, together with the summary receiver operating characteristic (SROC) curve plotted by calculating the area under the curve (AUC). Generated pooled summary estimates (95% CIs) were calculated for the evaluation of the overall accuracy of this study. Results. Five fourfold tables were made from the four studies that were included in the meta-analysis. The pooled sensitivity of Xpert Ebola was 0.98 (95% confidence interval (CI) (0.95, 0.99)), and the pooled specificity was 0.98 (95% CI (0.97, 0.99)). The pooled values of positive likelihood ratio was 53.91 (95% CI (12.82, 226.79)), with negative likelihood ratio being 0.04 (95% CI (0.02, 0.08)) and diagnostic odds ratio being 2649.45 (95% CI (629.61, 11149.02)). The AUC was 0.9961. Conclusions. Compared with RT-PCR, Xpert Ebola has high sensitivity and specificity. Therefore, it is a valued alternative method for the clinical diagnosis of Ebola virus infection. However, the Xpert Ebola test is a qualitative test that does not provide quantitative testing of EBOV concentration. Whether it can completely replace other methods or not calls for further evidences.


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