scholarly journals Antibody Quality and Protection from Lethal Ebola Virus Challenge in Nonhuman Primates Immunized with Rabies Virus Based Bivalent Vaccine

2013 ◽  
Vol 9 (5) ◽  
pp. e1003389 ◽  
Author(s):  
Joseph E. Blaney ◽  
Andrea Marzi ◽  
Mallory Willet ◽  
Amy B. Papaneri ◽  
Christoph Wirblich ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Bivalent Vaccine ◽  
Virus Challenge

scholarly journals Ebola Virus‐Like Particle–Based Vaccine Protects Nonhuman Primates against Lethal Ebola Virus Challenge

2007 ◽  
Vol 196 (s2) ◽  
pp. S430-S437 ◽  
Author(s):  
Kelly L. Warfield ◽  
Dana L. Swenson ◽  
Gene G. Olinger ◽  
Warren V. Kalina ◽  
M. Javad Aman ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Challenge ◽  
Virus Like Particle

scholarly journals A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles Protects Nonhuman Primates from Lethal Ebola Virus Challenge

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Arban Domi ◽  
Friederike Feldmann ◽  
Rahul Basu ◽  
Nathanael McCurley ◽  
Kyle Shifflett ◽  
...  
Keyword(s):  
Single Dose ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Like Particles ◽  
Virus Challenge

scholarly journals Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates

2013 ◽  
Vol 110 (5) ◽  
pp. 1893-1898 ◽  
Author(s):  
A. Marzi ◽  
F. Engelmann ◽  
F. Feldmann ◽  
K. Haberthur ◽  
W. L. Shupert ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Challenge

scholarly journals Evaluation in Nonhuman Primates of Vaccines against Ebola Virus

2002 ◽  
Vol 8 (5) ◽  
pp. 503-507 ◽  
Author(s):  
Thomas W. Geisbert ◽  
Peter Pushko ◽  
Kevin Anderson ◽  
Jonathan Smith ◽  
Kelly J. Davis ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Ebola Virus

scholarly journals Protection of Mice Against Lethal Rabies Virus Challenge Using Short Interfering RNAs (siRNAs) Delivered Through Lentiviral Vector

2013 ◽  
Vol 56 (2) ◽  
pp. 91-101 ◽  
Author(s):  
Niraj K. Singh ◽  
Chetan D. Meshram ◽  
Arvind A. Sonwane ◽  
Shyam S. Dahiya ◽  
Sachin S. Pawar ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Lentiviral Vector ◽  
Virus Challenge

scholarly journals Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study

The Lancet ◽  
2010 ◽  
Vol 375 (9729) ◽  
pp. 1896-1905 ◽  
Author(s):  
Thomas W Geisbert ◽  
Amy CH Lee ◽  
Marjorie Robbins ◽  
Joan B Geisbert ◽  
Anna N Honko ◽  
...  
Keyword(s):  
Rna Interference ◽  
Ebola Virus ◽  
Proof Of Concept ◽  
Virus Challenge ◽  
Concept Study

scholarly journals Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Hualei Wang ◽  
Gary Wong ◽  
Wenjun Zhu ◽  
Shihua He ◽  
Yongkun Zhao ◽  
...  
Keyword(s):  
Large Scale ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Virus Disease ◽  
Hemorrhagic Fever ◽  
West African ◽  
Clinical Testing ◽  
The Past ◽  
Over 40 Years

ABSTRACT Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly and quantities are limited; therefore, MAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal F(ab′)2 fragments from horses hyperimmunized with an EBOV vaccine. The F(ab′)2 was found to potently neutralize West African and Central African EBOV in vitro. Treatment of nonhuman primates (NHPs) with seven doses of 100 mg/kg F(ab′)2 beginning 3 or 5 days postinfection (dpi) resulted in a 100% survival rate. Notably, NHPs for which treatment was initiated at 5 dpi were already highly viremic, with observable signs of EBOV disease, which demonstrated that F(ab′)2 was still effective as a therapeutic agent even in symptomatic subjects. These results show that F(ab′)2 should be advanced for clinical testing in preparation for future EBOV outbreaks and epidemics. IMPORTANCE EBOV is one of the deadliest viruses to humans. It has been over 40 years since EBOV was first reported, but no cure is available. Research breakthroughs over the past 5 years have shown that MAbs constitute an effective therapy for EBOV infections. However, MAbs are expensive and difficult to produce in large amounts and therefore may only play a limited role during an epidemic. A cheaper alternative is required, especially since EBOV is endemic in several third world countries with limited medical resources. Here, we used a standard protocol to produce large amounts of antiserum F(ab′)2 fragments from horses vaccinated with an EBOV vaccine, and we tested the protectiveness in monkeys. We showed that F(ab′)2 was effective in 100% of monkeys even after the animals were visibly ill with EBOV disease. Thus, F(ab′)2 could be a very good option for large-scale treatments of patients and should be advanced to clinical testing.

scholarly journals Previremic Identification of Ebola or Marburg Virus Infection Using Integrated Host-Transcriptome and Viral Genome Detection

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Emily Speranza ◽  
Ignacio Caballero ◽  
Anna N. Honko ◽  
Joshua C. Johnson ◽  
J. Kyle Bohannon ◽  
...  
Keyword(s):  
Host Response ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Clinical Symptoms ◽  
Infectious Agent ◽  
Marburg Virus ◽  
Viral Rna ◽  
Molecular Tests ◽  
Early Replication ◽  
Host Infection

ABSTRACT Outbreaks of filoviruses, such as those caused by the Ebola (EBOV) and Marburg (MARV) virus, are difficult to detect and control. The initial clinical symptoms of these diseases are nonspecific and can mimic other endemic pathogens. This makes confident diagnosis based on clinical symptoms alone impossible. Molecular diagnostics for these diseases that rely on the detection of viral RNA in the blood are only effective after significant disease progression. As an approach to identify these infections earlier in the disease course, we tested the effectiveness of viral RNA detection combined with an assessment of sentinel host mRNAs that are upregulated following filovirus infection. RNAseq analysis of EBOV-infected nonhuman primates identified host RNAs that are upregulated at early stages of infection. NanoString probes that recognized these host-response RNAs were combined with probes that recognized viral RNA and were used to classify viral infection both prior to viremia and postviremia. This approach was highly successful at identifying samples from nonhuman primate subjects and correctly distinguished the causative agent in a previremic stage in 10 EBOV and 5 MARV samples. This work suggests that unified host response/viral fingerprint assays can enable diagnosis of disease earlier than testing for viral nucleic acid alone, which could decrease transmission events and increase therapeutic effectiveness. IMPORTANCE Current molecular tests that identify infection with high-consequence viruses such as Ebola virus and Marburg virus are based on the detection of virus material in the blood. These viruses do not undergo significant early replication in the blood and, instead, replicate in organs such as the liver and spleen. Thus, virus begins to accumulate in the blood only after significant replication has already occurred in those organs, making viremia an indicator of infection only after initial stages have become established. Here, we show that a multianalyte assay can correctly identify the infectious agent in nonhuman primates (NHPs) prior to viremia through tracking host infection response transcripts. This illustrates that a single-tube, sample-to-answer format assay could be used to advance the time at which the type of infection can be determined and thereby improve outcomes.

scholarly journals Next-Generation Sequencing Reveals a Controlled Immune Response to Zaire Ebola Virus Challenge in Cynomolgus Macaques Immunized with Vesicular Stomatitis Virus Expressing Zaire Ebola Virus Glycoprotein (VSVΔG/EBOVgp)

2015 ◽  
Vol 22 (3) ◽  
pp. 354-356 ◽  
Author(s):  
Fredrik Barrenas ◽  
Richard R. Green ◽  
Matthew J. Thomas ◽  
G. Lynn Law ◽  
Sean C. Proll ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Host Response ◽  
Ebola Virus ◽  
Mononuclear Cells ◽  
Transcriptional Response ◽  
Peripheral Blood Mononuclear ◽  
Virus Challenge ◽  
Cynomolgus Macaques ◽  
Vesicular Stomatitis ◽  
Generation Sequencing

ABSTRACTVesicular stomatitis virus expressing Zaire Ebola virus (EBOV) glycoprotein (VSVΔG/EBOVgp) could be used as a vaccine to meet the 2014 Ebola virus outbreak. To characterize the host response to this vaccine, we used mRNA sequencing to analyze peripheral blood mononuclear cells (PBMCs) from cynomolgus macaques after VSVΔG/EBOVgp immunization and subsequent EBOV challenge. We found a controlled transcriptional response that transitioned to immune regulation as the EBOV was cleared. This observation supports the safety of the vaccine.

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