#Recombinant subunit #vaccines protect guinea pigs from lethal #Ebola virus challenge (Vaccine, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vaccine. 2019 Jul 16. pii: S0264-410X(19)30797-2. doi: 10.1016/j.vaccine.2019.06.035. [Epub ahead of print]

Recombinant subunit vaccines protect guinea pigs from lethal Ebola virus challenge.

Lehrer AT1, Wong TS2, Lieberman MM3, Johns L2, Medina L3, Feldmann F4, Feldmann H5, Marzi A6.

Author information: 1 PanThera Biopharma, LLC, Aiea, HI 96701, United States; University of Hawaii at Manoa, John A. Burns School of Medicine, Honolulu, HI 96813, United States. Electronic address: lehrer@hawaii.edu. 2 PanThera Biopharma, LLC, Aiea, HI 96701, United States; University of Hawaii at Manoa, John A. Burns School of Medicine, Honolulu, HI 96813, United States. 3 University of Hawaii at Manoa, John A. Burns School of Medicine, Honolulu, HI 96813, United States. 4 Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, United States. 5 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, United States. 6 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, United States. Electronic address: marzia@niaid.nih.gov.

 

Abstract

Ebola virus (EBOV) is among the deadliest pathogens known to man causing infrequent outbreaks of hemorrhagic disease. In humans, the case fatality rates in the outbreaks can reach 90%. During the West African epidemic almost 30,000 people were infected and of these over 11,000 fatalities were reported. Currently, we are facing an uncontained larger outbreak in the Democratic Republic of the Congo. Even though EBOV was discovered in 1976, extensive efforts to develop countermeasures, particularly therapeutics and vaccines, started late and there is still no FDA-approved product available. Nevertheless, one candidate vaccine, the rVSV-ZEBOV, is being used in clinical trials during the current outbreak with the hope of ending the human transmission chains. However, adverse reactions to administration of some EBOV vaccines have been reported; therefore, we have developed a safe and efficacious formulation of insect-cell derived adjuvanted protein vaccines. Vaccine candidates containing the EBOV glycoprotein with or without matrix proteins VP24 and VP40 formulated with one of three different adjuvants were tested in guinea pigs for immunogenicity and efficacy against lethal EBOV challenge. The results demonstrated that these vaccine candidates engendered high titers of antigen-specific antibodies in immunized animals and two of these vaccine candidates afforded complete or nearly complete protection against lethal challenge. Interestingly, we found a sex bias in partially protected immunized groups with male guinea pigs succumbing to disease and females surviving. In summary, we developed a safe and immunogenic adjuvanted subunit vaccine uniformly protective against EBOV disease in guinea pigs.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS: Glycoprotein; Recombinant protein; VP24; VP40; Zaire ebolavirus

PMID: 31324500 DOI: 10.1016/j.vaccine.2019.06.035

Keywords: Ebola; ZEBOV; Vaccines; Animal models.

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The efficacy of poly-ICLC against #Ebola-Zaire virus (EZV) #infection in mice and cynomolgus #monkeys (Antiviral Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Antiviral Res. 2019 Jan 3. pii: S0166-3542(18)30407-8. doi: 10.1016/j.antiviral.2018.12.020. [Epub ahead of print]

The efficacy of poly-ICLC against Ebola-Zaire virus (EZV) infection in mice and cynomolgus monkeys.

Kende M1, Paragas J2, Salazar AM3.

Author information: 1 United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD, 21702, United States. Electronic address: meir.kende.vol@mail.mil. 2 United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD, 21702, United States. 3 Oncovir, Inc., 3203 Cleveland Avenue, Washington D.C, 20008, United States.

 

Abstract

The potential protection of poly-ICLC (Hiltonol®) a double stranded RNA (dsRNA) against EZV infection was assessed with prophylactic and therapeutic administration to wild type and TLR3-negative mice, and in non-human primates (NHPs) by measuring EZV serum titers, survival extension, and serum liver and kidney function markers. Various doses of aqueous and liposomal poly-ICLC monotherapy provided robust protection in otherwise lethal murine Ebola virus challenge models, when treatment is started on the day of -or one day after virus challenge. There was no advantage of liposomal vs. the aqueous poly-ICLC form. Protection appeared to be independent of TLR-3. NHPs treated with poly-ICLC and challenged with EZV survived longer but eventually succumbed to Ebola infection. Nevertheless, the liver and kidney serum markers were markedly reduced in the infected and treated NHPs. In the two longest surviving poly-ICLC- treated NHPs, the day 10 serum EZV titer was reduced 2.1 and 30 fold respectively.

KEYWORDS: Aqueous/liposomal poly-ICLC; Efficacy in mice; NHP EZV titers; NHP liver/kidney enzymes; NHP survival time; TLR+/ TLR-3 mice

PMID: 30611774 DOI: 10.1016/j.antiviral.2018.12.020

Keywords: Ebola; Antivirals; Animal models.

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Comparative Transcriptomics in #Ebola #Makona-Infected #Ferrets, Nonhuman #Primates, and #Humans (J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Infect Dis. 2018 Nov 22;218(suppl_5):S486-S495. doi: 10.1093/infdis/jiy455.

Comparative Transcriptomics in Ebola Makona-Infected Ferrets, Nonhuman Primates, and Humans.

Cross RW1,2, Speranza E3, Borisevich V1,2, Widen SG4, Wood TG4, Shim RS5, Adams RD5, Gerhardt DM5, Bennett RS5, Honko AN5, Johnson JC5, Hensley LE5, Geisbert TW1,2, Connor JH4,3.

Author information: 1 Galveston National Laboratory, University of Texas Medical Branch, Galveston. 2 Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston. 3 Department of Microbiology, Bioinformatics Program, National Emerging Infectious Disease Laboratories, Boston University, Massachusetts. 4 Departments of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston. 5 Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland.

 

Abstract

The domestic ferret is a uniformly lethal model of infection for 3 species of Ebolavirus known to be pathogenic in humans. Reagents to systematically analyze the ferret host response to infection are lacking; however, the recent publication of a draft ferret genome has opened the potential for transcriptional analysis of ferret models of disease. In this work, we present comparative analysis of longitudinally sampled blood taken from ferrets and nonhuman primates infected with lethal doses of the Makona variant of Zaire ebolavirus. Strong induction of proinflammatory and prothrombotic signaling programs were present in both ferrets and nonhuman primates, and both transcriptomes were similar to previously published datasets of fatal cases of human Ebola virus infection.

PMID: 30476250 DOI: 10.1093/infdis/jiy455

Keywords: Ebola; Ebola-Makona; Animal models.

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#Survey of #Ebola Viruses in Frugivorous and Insectivorous #Bats in #Guinea, #Cameroon, and the #DRC, 2015–2017 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 24, Number 12—December 2018 / Research

Survey of Ebola Viruses in Frugivorous and Insectivorous Bats in Guinea, Cameroon, and the Democratic Republic of the Congo, 2015–2017

Helene M. De Nys1, Placide Mbala Kingebeni1, Alpha K. Keita1, Christelle Butel, Guillaume Thaurignac, Christian-Julian Villabona-Arenas, Thomas Lemarcis, Mare Geraerts, Nicole Vidal, Amandine Esteban, Mathieu Bourgarel, François Roger, Fabian Leendertz, Ramadan Diallo, Simon-Pierre Ndimbo-Kumugo, Justus Nsio-Mbeta, Nikki Tagg, Lamine Koivogui, Abdoulaye Toure, Eric Delaporte, Steve Ahuka-Mundeke, Jean-Jacques Muyembe Tamfum, Eitel Mpoudi-Ngole, Ahidjo Ayouba2, and Martine Peeters2

Author affiliations: TransVIHMI of Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale and University of Montpellier, Montpellier, France (H.M. De Nys, P. Mbala Kingebeni, A.K. Keita, C. Butel, G. Thaurignac, C.-J. Villabona-Arenas, T. Lemarcis, M. Geraerts, N. Vidal, A. Esteban, M. Bourgarel, F. Roger, A. Toure, E. Delaporte, A. Ayouba, M. Peeters); National Institute of Biomedical Research, Kinshasa, Democratic Republic of the Congo (P. Mbala Kingebeni, S.P. Ndimbo-Kumugo, S. Ahuka-Mundeke, J.-J. Muyembe Tamfum); Cliniques Universitaires de Kinshasa, Kinshasa (P. Mbala Kingebeni, S. Ahuka-Mundeke, J.-J. Muyembe Tamfum); Centre de Recherche et de Formation en Infectiologie de Guinée, Conakry, Guinea (A.K. Keita, A. Toure); Robert Koch-Institute, Berlin, Germany (F. Leendertz); Ministère de l’Elevage et des Productions Animales, Conakry (R. Diallo); Direction de Lutte contre la Maladie, Kinshasa (J. Nsio-Mbeta); Royal Zoological Society of Antwerp, Antwerp, Belgium (N. Tagg); Université de Conakry, Conakry (L. Koivogui); Institut National de Sante Publique, Conakry (A. Toure); Institut de Recherches Médicales et d’Études des Plantes Médicinales, Yaoundé, Cameroon (E. Mpoudi-Ngole); Cameroon Institut de Recherche pout le Développement, Yaoundé (E. Mpoudi-Ngole)

 

Abstract

To clarify the role of bats in the ecology of Ebola viruses, we assessed the prevalence of Ebola virus antibodies in a large-scale sample of bats collected during 2015–2017 from countries in Africa that have had previous Ebola outbreaks (Guinea, the Democratic Republic of the Congo) or are at high risk for outbreaks (Cameroon). We analyzed 4,022 blood samples of bats from >12 frugivorous and 27 insectivorous species; 2–37 (0.05%–0.92%) bats were seropositive for Zaire and 0–30 (0%–0.75%) bats for Sudan Ebola viruses. We observed Ebola virus antibodies in 1 insectivorous bat genus and 6 frugivorous bat species. Certain bat species widespread across Africa had serologic evidence of Zaire and Sudan Ebola viruses. No viral RNA was detected in the subset of samples tested (n = 665). Ongoing surveillance of bats and other potential animal reservoirs are required to predict and prepare for future outbreaks.

Keywords: Ebolavirus; Sudan Virus; Ebola Zaire; Bats; Guinea; DRC; Cameroon.

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Rapid confirmation of the #ZEBOV in the #outbreak of the #Equateur province in #DRC: implications for #publichealth interventions (Clin Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2018 Jun 29. doi: 10.1093/cid/ciy527. [Epub ahead of print]

Rapid confirmation of the Zaire Ebola Virus in the outbreak of the Equateur province in the Democratic Republic of Congo: implications for public health interventions.

Mbala Kingebeni P1,2,3, Villabona-Arenas CJ3, Vidal N3, Likofata J4, Nsio-Mbeta J5, Makiala-Mandanda S1,2, Mukadi D1,2, Mukadi P1,2, Kumakamba C1,2, Djokolo B5, Ayouba A3, Delaporte E3, Peeters M3, Muyembe Tamfum JJ1,2, Ahuka Mundeke S1,2.

Author information: 1 National Institute of Biomedical Research (INRB), Kinshasa, Democratic Republic of the Congo. 2 Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of Congo. 3 TransVIHMI ; Institut de Recherche pour le Développement, University of Montpellier, INSERM, Montpellier, France. 4 Laboratoire Provinciale, Mbandaka, Democratic Republic of the Congo. 5 Direction Générale de Lutte contre la Maladie (DLM), Kinshasa, Democratic Republic of Congo.

 

Abstract

Ten days after the declaration of the Ebola outbreak in the Equateur Province of the Democratic Republic of Congo, rapid identification of the species Zaire Ebolavirus (EBOV) using partial gene amplification and nanopore sequencing backed up the use of the rVSV-ZEBOV vaccine in the ring vaccination strategy recommended by WHO.

PMID: 29961823 DOI: 10.1093/cid/ciy527

Keywords: Ebola; Ebola-Zaire Virus; DRC.

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Broad Neutralizing Activity Against #Ebolaviruses Lacking the #Mucin-Like Domain in #Convalescent #Plasma Specimens From #Patients With Ebola Virus Disease (J Infect Dis., abstract)

[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Broad Neutralizing Activity Against Ebolaviruses Lacking the Mucin-Like Domain in Convalescent Plasma Specimens From Patients With Ebola Virus Disease

Joanna Luczkowiak, Fatima Lasala, Marta Mora-Rillo, Jose R Arribas, Rafael Delgado

The Journal of Infectious Diseases, jiy302, https://doi.org/10.1093/infdis/jiy302

Published: 25 June 2018

 

Abstract

Background

In Ebola virus (EBOV) infection, the specific neutralizing activity of convalescent plasma against other members of the Ebolavirus genus has not been extensively analyzed.

Methods

We measured the neutralizing activity in plasma from 3 survivors of the recent outbreak due to the Makona variant of EBOV and tested its neutralizing potency against other variants of EBOV (ie, Mayinga and Kikwit) and against Sudan virus (SUDV), Bundibugyo virus (BDBV), and Reston virus (RESTV), using a glycoprotein (GP)–pseudotyped lentiviral system both with full-length GP and in vitro–cleaved GP (GPCL).

Results

Convalescent plasma specimens from survivors of EBOV infection showed low neutralizing activity against full-length GPs of SUDV, BDBV, RESTV, and EBOV variants Mayinga and Kikwit. However, broad and potent neutralizing activity was observed against the GPCL forms of SUDV, BDBV, and RESTV.

Discussion

Removal of the mucin-like domain and glycan cap from the GP of members of the Ebolavirus genus presumably exposes conserved epitopes in or in the vicinity of the receptor binding site and internal fusion loop that are readily amenable to neutralization. These types of broad neutralizing antibodies could be induced by using immunogens mimicking GPCL.

Ebola virus, glycoprotein, convalescent patients, neutralization assay

Issue Section: Supplement Article

Keywords: Filovirus; Ebola; Ebola-Makona; Neutralizing Antibodies.

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Development of #clinical-stage #human #monoclonal #antibodies that treat advanced #Ebola virus disease in non-human primates (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Development of clinical-stage human monoclonal antibodies that treat advanced Ebola virus disease in non-human primates

Kristen E Pascal, Drew Dudgeon, John C Trefry, Manu Anantpadma, Yasuteru Sakurai, Charles D Murin, Hannah L Turner, Jeanette Fairhurst, Marcela Torres, Ashique Rafique, Ying Yan, Ashok Badithe, Kevin Yu, Terra Potocky, Sandra L Bixler, Taylor B Chance, William D Pratt, Franco D Rossi, Joshua D Shamblin, Suzanne E Wollen, Justine M Zelko, Ricardo Carrion, Jr, Gabriella Worwa, Hilary M Staples, Darya Burakov, Robert Babb, Gang Chen, Joel Martin, Tammy T Huang, Karl Erlandson, Melissa S Willis, Kimberly Armstrong, Thomas M Dreier, Andrew B Ward, Robert A Davey, Margaret L M Pitt, Leah Lipsich, Peter Mason, William Olson, Neil Stahl, Christos A Kyratsous

The Journal of Infectious Diseases, jiy285, https://doi.org/10.1093/infdis/jiy285

Published: 31 May 2018

 

Abstract

Background

For most classes of drugs rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety and PK profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases.

Methods

Here we deployed a platform to generate, test and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-EBOV antibodies by immunizing VelocImmune® mice that use human Ig variable regions in their humoral responses.

Results

Of the antibody clones isolated, three were selected as best at neutralizing EBOV and triggering FcRIIIa. Binding studies and negative-stain electron microscopy revealed that the three selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the three antibodies protected non-human primates from EBOV disease even after disease symptoms were apparent.

Conclusions

This antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities and demonstrates high-level post-exposure protection from lethal EBOV disease in NHP. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.

Filovirus, Zaire ebolavirus, EBOV, monoclonal antibodies, non human primates, treatment

Issue Section: Supplement Article

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Keywords: Ebola; Monoclonal Antibodies.

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