In vitro characterization and in vivo effectiveness of #Ebola virus specific #equine #polyclonal F(ab’)2 (J Infect Dis., abstract)

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

In vitro characterization and in vivo effectiveness of Ebola virus specific equine polyclonal F(ab’)2

Trina Racine, Mélanie Denizot, Delphine Pannetier, Ludovic Nguyen, Anaïs Pasquier, Hervé Raoul, Jean-François Saluzzo, Gary Kobinger, Francisco Veas, Cécile H Herbreteau

The Journal of Infectious Diseases, jiz068, https://doi.org/10.1093/infdis/jiz068

Published: 14 February 2019

 

Abstract

There is no vaccine or approved therapy against lethal Ebola virus (EBOV). We investigated a proven technology platform to produce polyclonal IgG fragments, F(ab’)2, against EBOV. Horses immunized with virus-like-particles (VLPs) harboring surface glycoprotein trimers of EBOV-Zaire/Makona produced anti-Ebola IgG polyclonal antibodies with high neutralization activity. Highly-purified equine anti-Ebola F(ab’)2 showed strong cross-neutralization of two Zaire EBOV strains (Gabon 2001 and Makona) and in vivothree or five daily F(ab’)2 intraperitoneal injections provided 100% protection to BALB/c mice against lethal EBOV challenge. Rapid preparation of purified equine anti-Ebola F(ab’)2 offers a potentially efficient therapeutic approach against EBOV disease in humans.

Ebola, immunoglobulins, equine, F(ab’)2 fragments

Issue Section: Brief Report

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Keywords: Ebola; Ebola Makona; Immunoglobulins.

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Unrecognised #Ebola virus #infection in #contact persons: what can we learn from it? (Lancet Infect Dis., summary)

[Source: The Lancet Infectious Diseases, full page: (LINK). Summary, edited.]

Unrecognised Ebola virus infection in contact persons: what can we learn from it?

Tom E Fletcher, Hilary Bower

Published: February 11, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30689-3

 

Summary

The epidemic of Ebola virus disease in west Africa in 2014–16 was the largest and most complex the world has ever seen. The four pillars of Ebola response include: case management, case finding and contact tracing, safe and dignified burial, and social mobilisation and community engagement. These four pillars are being implemented in the current outbreak in the Democratic Republic of the Congo (DRC), which is further complicated by its location in a conflict zone. 1 Increased understanding of disease pathogenesis and the evaluation of novel therapeutics and vaccine candidates has informed current control measures, while access to survivors and their contacts in west Africa has also provided a unique opportunity to research filovirus transmission.

Keywords: Ebola; West Africa; DRC.

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#Prevalence of #infection among #asymptomatic and #paucisymptomatic #contact persons exposed to #Ebola virus in #Guinea: a retrospective, cross-sectional observational study (Lancet Infect Dis., abstract)

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

Prevalence of infection among asymptomatic and paucisymptomatic contact persons exposed to Ebola virus in Guinea: a retrospective, cross-sectional observational study

Mamadou Saliou Kalifa Diallo, MSc *, Muriel Rabilloud, PhD *, Prof Ahidjo Ayouba, PhD *, Prof Abdoulaye Touré, PhD *, Guillaume Thaurignac, MSc, Alpha Kabinet Keita, PhD, Christelle Butel, MSc., Cécé Kpamou, MSc, Thierno Alimou Barry, MD, Mariama Djouldé Sall, MD, Ibrahima Camara, MSc, Sandrine Leroy, PhD, Prof Philippe Msellati, PhD, Prof René Ecochard, PhD, Prof Martine Peeters, PhD, Prof Mamadou Saliou Sow, PhD, Prof Eric Delaporte, PhD, Prof Jean-François Etard, PhD  on behalf of theContactebogui Study Group †

Published: February 11, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30649-2

 

Summary

Background

The prevalence of Ebola virus infection among people who have been in contact with patients with Ebola virus disease remains unclear, but is essential to understand the dynamics of transmission. This study aimed to identify risk factors for seropositivity and to estimate the prevalence of Ebola virus infection in unvaccinated contact persons.

Methods

In this retrospective, cross-sectional observational study, we recruited individuals between May 12, 2016, and Sept 8, 2017, who had been in physical contact with a patient with Ebola virus disease, from four medical centres in Guinea (Conakry, Macenta, N’zérékoré, and Forécariah). Contact persons had to be 7 years or older and not diagnosed with Ebola virus disease. Participants were selected through the Postebogui survivors’ cohort. We collected self-reported information on exposure and occurrence of symptoms after exposure using a questionnaire, and tested antibody response against glycoprotein, nucleoprotein, and 40-kDa viral protein of Zaire Ebola virus by taking a blood sample. The prevalence of Ebola virus infection was estimated with a latent class model.

Findings

1721 contact persons were interviewed and given blood tests, 331 of whom reported a history of vaccination so were excluded, resulting in a study population of 1390. Symptoms were reported by 216 (16%) contact persons. The median age of participants was 26 years (range 7–88) and 682 (49%) were male. Seropositivity was identified in 18 (8·33%, 95% CI 5·01–12·80) of 216 paucisymptomatic contact persons and 39 (3·32%, 5·01–12·80) of 1174 (2–4) asymptomatic individuals (p=0·0021). Seropositivity increased with participation in burial rituals (adjusted odds ratio [aOR] 2·30, 95% CI 1·21–4·17; p=0·0079) and exposure to blood or vomit (aOR 2·15, 1·23–3·91; p=0·0090). Frequency of Ebola virus infection varied from 3·06% (95% CI 1·84–5·05) in asymptomatic contact persons who did not participate in burial rituals to 5·98% (2·81–8·18) in those who did, and from 7·17% (3·94–9·09) in paucisymptomatic contact persons who did not participate in burial rituals to 17·16% (12·42–22·31) among those who did.

Interpretation

This study provides a new assessment of the prevalence of Ebola virus infection among contact persons according to exposure, provides evidence for the occurrence of paucisymptomatic cases, and reinforces the importance of closely monitoring at-risk contact persons.

Funding

Institut National de la Santé et de la Recherche Médicale, Reacting, the French Ebola Task Force, Institut de Recherche pour le Développement, and Montpellier University Of Excellence-University of Montpellier.

Keywords: Ebola; Guinea; Seroprevalence.

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Early #human B cell response to #Ebola virus in four #US #survivors of #infection (J Virol., abstract)

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

J Virol. 2019 Feb 6. pii: JVI.01439-18. doi: 10.1128/JVI.01439-18. [Epub ahead of print]

Early human B cell response to Ebola virus in four U.S. survivors of infection.

Williamson L1, Flyak AI1, Kose N1, Bombardi R1, Branchizio A1, Reddy S2, Davidson E2, Doranz B2, Fusco ML3, Saphire EO3, Halfmann PJ4, Kawaoka Y4, Piper AE5, Glass PJ5, Crowe JE Jr6,1,1.

Author information: 1 Departments of Pathology, Microbiology, and Immunology Pediatrics, and The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA. 2 Integral Molecular, Philadelphia, PA, 19104, USA. 3 Departments of Immunology and Microbial Science, The Scripps Research Institute La Jolla, CA 92037, USA. 4 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA. 5 Virology Division, US Army Medical Research Institute of Infectious Diseases, MD 21702, USA. 6 Departments of Pathology, Microbiology, and Immunology Pediatrics, and The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA james.crowe@vanderbilt.edu.

 

Abstract

The human B cell response to natural filovirus infections early after recovery is poorly understood. Previous serologic studies suggest that some Ebola virus survivors exhibit delayed antibody responses with low magnitude and quality. Here, we sought to study the population of individual memory B cells induced early in convalescence. We isolated monoclonal antibodies (mAbs) from memory B cells from four survivors treated for Ebola virus disease (EVD) one or three-months after discharge from hospital. At the early time points post-recovery, the frequency of Ebola-specific B cells was low and dominated by clones that were cross-reactive with both Ebola glycoprotein (GP) and with the secreted form (sGP). Of 25 mAbs isolated from four donors, only one exhibited neutralization activity. This neutralizing mAb, designated mAb EBOV237, recognizes an epitope in the glycan cap of the surface glycoprotein. In vivo murine lethal challenge studies showed that EBOV237 conferred protection when given prophylactically at a level similar to that of the ZMapp component mAb 13C6. The results suggest that the human B cell response to EVD one to three months post-discharge is characterized by a paucity of broad or potent neutralizing clones. However, the neutralizing epitope in the glycan cap recognized by EBOV237 may play a role in the early human antibody response to EVD and should be considered in rational design strategies for new Ebola virus vaccine candidates.

 

IMPORTANCE

The pathogenesis of Ebola virus disease (EVD) in humans is complex, and the mechanisms contributing to immunity are poorly understood. In particular, it appears that the quality and magnitude of the human B cell response early after recovery from EVD may be reduced compared to most viral infections. Here we isolated human monoclonal antibodies from B cells of four survivors of EVD at one or three months after hospital discharge. Ebola-specific memory B cells early in convalescence were low in frequency, and the antibodies they encoded demonstrated poor neutralizing potencies. One neutralizing antibody that protected mice from lethal infection, EBOV237, was identified in the panel of 25 human antibodies isolated. Recognition of the glycan cap epitope recognized by EBOV237 suggests this antigenic site should be considered in vaccine design and treatment strategies for EVD.

Copyright © 2019 American Society for Microbiology.

PMID: 30728263 DOI: 10.1128/JVI.01439-18

Keywords: Ebola; Monoclonal antibodies.

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Effect of #sexual #transmission on the West #Africa #Ebola #outbreak in 2014: a mathematical modelling study (Sci Rep., abstract)

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

Sci Rep. 2019 Feb 7;9(1):1653. doi: 10.1038/s41598-018-38397-3.

Effect of sexual transmission on the West Africa Ebola outbreak in 2014: a mathematical modelling study.

Luo D1, Zheng R2, Wang D3, Zhang X4, Yin Y4, Wang K5, Wang W6.

Author information: 1 Department of Student Affairs, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, 830011, P. R. China. 2 Department of Infectious Diseases, The first Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, P. R. China. 3 Biostatistics Unit, Department of Clinical Sciences, Liverpool School of Tropical Medicine Pembroke Place, Liverpool, L3 5QA, UK. 4 College of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, 830011, P. R. China. 5 College of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, 830011, P. R. China. wangkaimath@sina.com. 6 School of Mathematics Science, Huaiyin Normal University, Huaiyin, 223300, P. R. China.

 

Abstract

The outbreak of the Ebola virus has resulted in significant morbidity and mortality in the affected areas, and Ebola virus RNA has been found in the semen of the survivors after 9 months of symptom onset. However, the role that sexual transmission played in the transmission is not very clear. In this paper, we developed a compartmental model for Ebola virus disease (EVD) dynamics, which includes three different infectious routes: contact with the infectious, contact with dead bodies, and transmission by sexual behaviour with convalescent survivors. We fitted the model to daily cumulative cases from the first reported infected case to October 25, 2014 for the epidemic in Sierra Leone, Liberia and Guinea. The basic reproduction numbers in these countries were estimated as 1.6726 (95%CI:1.5922-1.7573), 1.8162 (95%CI:1.7660-1.8329) and 1.4873 (95%CI:1.4770-1.4990), respectively. We calculated the contribution of sexual transmission to the basic reproduction number R0 as 0.1155 (6.9%), 0.0236 (2.8%) and 0.0546 (3.7%) in Sierra Leone, Liberia and Guinea, respectively. Sensitivity analysis shows that the transmission rates caused by contacts with alive patients and sexual activities with convalescent patients have stronger impacts on the R0. These results suggest that isolating the infectious individuals and advising the recovery men to avoid sexual intercourse are efficient ways for the eradication of endemic EVD.

PMID: 30733561 DOI: 10.1038/s41598-018-38397-3

Keywords: Ebola; West Africa; Mathematical models.

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#Filovirus #Virulence in #Interferon α/β and γ Double Knockout Mice, and #Treatment with #Favipiravir (Viruses, abstract)

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

Viruses. 2019 Feb 3;11(2). pii: E137. doi: 10.3390/v11020137.

Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir.

Comer JE1,2,3,4, Escaffre O5, Neef N6, Brasel T7,8,9, Juelich TL10, Smith JK11, Smith J12, Kalveram B13, Perez DD14, Massey S15, Zhang L16, Freiberg AN17,18,19,20.

Author information: 1 Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. jscomer@UTMB.edu. 2 Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. jscomer@UTMB.edu. 3 Sealy Institute for Vaccine Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. jscomer@UTMB.edu. 4 The Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. jscomer@UTMB.edu. 5 Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. olescaff@utmb.edu. 6 Experimental Pathology Laboratories, Inc., Sterling, VA 20167, USA. nneef@7thwavelabs.com. 7 Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. trbrasel@utmb.edu. 8 Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. trbrasel@utmb.edu. 9 Sealy Institute for Vaccine Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. trbrasel@utmb.edu. 10 Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. tljuelic@utmb.edu. 11 Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. jeksmith@UTMB.EDU. 12 Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. jensmit1@utmb.edu. 13 Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. bkkalver@utmb.edu. 14 Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. dadperez@tamu.edu. 15 Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. chmassey@utmb.edu. 16 Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. lihzhang@utmb.edu. 17 Sealy Institute for Vaccine Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. anfreibe@utmb.edu. 18 The Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. anfreibe@utmb.edu. 19 Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. anfreibe@utmb.edu. 20 Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. anfreibe@utmb.edu.

 

Abstract

The 2014 Ebolavirus outbreak in West Africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would facilitate the screening of anti-filovirus agents. To that end, we characterized knockout mice lacking α/β and γ interferon receptors (IFNAGR KO) as a model for wild-type filovirus infection. Intraperitoneal challenge of IFNAGR KO mice with several known human pathogenic species from the genus Ebolavirus and Marburgvirus, except Bundibugyo ebolavirus and Taï Forest ebolavirus, caused variable mortality rate. Further characterization of the prototype Ebola virus Kikwit isolate infection in this KO mouse model showed 100% lethality down to a dilution equivalent to 1.0 × 10-1 pfu with all deaths occurring between 7 and 9 days post-challenge. Viral RNA was detectable in serum after challenge with 1.0 × 10² pfu as early as one day after infection. Changes in hematology and serum chemistry became pronounced as the disease progressed and mirrored the histological changes in the spleen and liver that were also consistent with those described for patients with Ebola virus disease. In a proof-of-principle study, treatment of Ebola virus infected IFNAGR KO mice with favipiravir resulted in 83% protection. Taken together, the data suggest that IFNAGR KO mice may be a useful model for early screening of anti-filovirus medical countermeasures.

KEYWORDS: Ebola virus; filovirus; interferon receptor knockout; mouse

PMID: 30717492 DOI: 10.3390/v11020137 Free full text

Keywords: Filovirus; Ebola; Marburg; Ebola Bundibugyo; Tai Forest Virus; Favipiravir; Antivirals; Animal models.

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Exploring the #contribution of #exposure heterogeneity to the #cessation of the 2014 #Ebola #epidemic (PLoS One, abstract)

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

PLoS One. 2019 Feb 1;14(2):e0210638. doi: 10.1371/journal.pone.0210638. eCollection 2019.

Exploring the contribution of exposure heterogeneity to the cessation of the 2014 Ebola epidemic.

Uekermann F1, Simonsen L2, Sneppen K1.

Author information: 1 Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark. 2 Department of Science and Enviroment, Roskilde University, Roskilde, Denmark.

 

Abstract

The unexpected early cessation of the recent West Africa Ebola outbreak demonstrated shortcomings of popular forecasting approaches and has not been fully understood yet. A popular hypothesis is that public health interventions mitigated the spread, such as ETUs and safe burials. We investigate whether risk heterogeneity within the population could serve as an alternative explanation. We introduce a model for spread in heterogeneous host population that is particularly well suited for early predictions due to its simplicity and ease of application. Furthermore, we explore the conditions under which the observed epidemic trajectory can be explained without taking into account the effect of public health interventions. While the obtained fits closely match the total case count time series, closer inspection of sub-population results made us conclude that risk heterogeneity is unlikely to fully explain the early cessation of Ebola; other factors such as behavioral changes and other interventions likely played a major role. More accurate predictions in a future scenario require models that allow for early sub-exponential growth, as well as access to additional data on patient occupation (risk level) and location, to allow identify local phenomena that influence spreading behavior.

PMID: 30707729 DOI: 10.1371/journal.pone.0210638 Free full text

Keywords: Ebola; West Africa; Society.

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