2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo

a retrospective genomic characterisation

Placide Mbala-Kingebeni, Catherine B. Pratt, Michael R Wiley, Moussa M. Diagne, Sheila Makiala-Mandanda, Amuri Aziza, Nicholas Di Paola, Joseph A. Chitty, Mamadou Diop, Ahidjo Ayouba, Nicole Vidal, Ousmane Faye, Oumar Faye, Stormy Karhemere, Aaron Aruna, Justus Nsio, Felix Mulangu, Daniel Mukadi, Patrick Mukadi, John Kombe & 20 others Anastasie Mulumba, Sophie Duraffour, Jacques Likofata, Elisabeth Pukuta, Katie Caviness, Maggie L. Bartlett, Jeanette Gonzalez, Timothy Minogue, Shanmuga Sozhamannan, Stephen M. Gross, Gary P. Schroth, Jens H. Kuhn, Eric F. Donaldson, Eric Delaporte, Mariano Sanchez-Lockhart, Martine Peeters, Jean Jacques Muyembe-Tamfum, Amadou Alpha Sall, Gustavo Palacios, Steve Ahuka-Mundeke

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: The 2018 Ebola virus disease (EVD)outbreak in Équateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures). Methods: We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 Équateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp. Findings: A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name “Tumba”. This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10−3 substitutions per site per year with “Tumba” vs 1·06 × 10−3 substitutions per site per year without “Tumba”). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail. Interpretation: Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures. Funding: Defense Biological Product Assurance Office.

Original languageEnglish (US)
Pages (from-to)641-647
Number of pages7
JournalThe Lancet Infectious Diseases
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2019

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Ebola Hemorrhagic Fever
Democratic Republic of the Congo
Ebolavirus
Disease Outbreaks
Genome
Nucleic Acid Databases
Computer Simulation
Vaccines
Membrane Glycoproteins
Genomics
Biological Products
Names
Flow Cytometry
Monoclonal Antibodies
Amino Acids
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo : a retrospective genomic characterisation. / Mbala-Kingebeni, Placide; Pratt, Catherine B.; Wiley, Michael R; Diagne, Moussa M.; Makiala-Mandanda, Sheila; Aziza, Amuri; Di Paola, Nicholas; Chitty, Joseph A.; Diop, Mamadou; Ayouba, Ahidjo; Vidal, Nicole; Faye, Ousmane; Faye, Oumar; Karhemere, Stormy; Aruna, Aaron; Nsio, Justus; Mulangu, Felix; Mukadi, Daniel; Mukadi, Patrick; Kombe, John; Mulumba, Anastasie; Duraffour, Sophie; Likofata, Jacques; Pukuta, Elisabeth; Caviness, Katie; Bartlett, Maggie L.; Gonzalez, Jeanette; Minogue, Timothy; Sozhamannan, Shanmuga; Gross, Stephen M.; Schroth, Gary P.; Kuhn, Jens H.; Donaldson, Eric F.; Delaporte, Eric; Sanchez-Lockhart, Mariano; Peeters, Martine; Muyembe-Tamfum, Jean Jacques; Alpha Sall, Amadou; Palacios, Gustavo; Ahuka-Mundeke, Steve.

In: The Lancet Infectious Diseases, Vol. 19, No. 6, 01.06.2019, p. 641-647.

Research output: Contribution to journalArticle

Mbala-Kingebeni, P, Pratt, CB, Wiley, MR, Diagne, MM, Makiala-Mandanda, S, Aziza, A, Di Paola, N, Chitty, JA, Diop, M, Ayouba, A, Vidal, N, Faye, O, Faye, O, Karhemere, S, Aruna, A, Nsio, J, Mulangu, F, Mukadi, D, Mukadi, P, Kombe, J, Mulumba, A, Duraffour, S, Likofata, J, Pukuta, E, Caviness, K, Bartlett, ML, Gonzalez, J, Minogue, T, Sozhamannan, S, Gross, SM, Schroth, GP, Kuhn, JH, Donaldson, EF, Delaporte, E, Sanchez-Lockhart, M, Peeters, M, Muyembe-Tamfum, JJ, Alpha Sall, A, Palacios, G & Ahuka-Mundeke, S 2019, '2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation', The Lancet Infectious Diseases, vol. 19, no. 6, pp. 641-647. https://doi.org/10.1016/S1473-3099(19)30124-0
Mbala-Kingebeni, Placide ; Pratt, Catherine B. ; Wiley, Michael R ; Diagne, Moussa M. ; Makiala-Mandanda, Sheila ; Aziza, Amuri ; Di Paola, Nicholas ; Chitty, Joseph A. ; Diop, Mamadou ; Ayouba, Ahidjo ; Vidal, Nicole ; Faye, Ousmane ; Faye, Oumar ; Karhemere, Stormy ; Aruna, Aaron ; Nsio, Justus ; Mulangu, Felix ; Mukadi, Daniel ; Mukadi, Patrick ; Kombe, John ; Mulumba, Anastasie ; Duraffour, Sophie ; Likofata, Jacques ; Pukuta, Elisabeth ; Caviness, Katie ; Bartlett, Maggie L. ; Gonzalez, Jeanette ; Minogue, Timothy ; Sozhamannan, Shanmuga ; Gross, Stephen M. ; Schroth, Gary P. ; Kuhn, Jens H. ; Donaldson, Eric F. ; Delaporte, Eric ; Sanchez-Lockhart, Mariano ; Peeters, Martine ; Muyembe-Tamfum, Jean Jacques ; Alpha Sall, Amadou ; Palacios, Gustavo ; Ahuka-Mundeke, Steve. / 2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo : a retrospective genomic characterisation. In: The Lancet Infectious Diseases. 2019 ; Vol. 19, No. 6. pp. 641-647.
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abstract = "Background: The 2018 Ebola virus disease (EVD)outbreak in {\'E}quateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures). Methods: We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 {\'E}quateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp. Findings: A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name “Tumba”. This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10−3 substitutions per site per year with “Tumba” vs 1·06 × 10−3 substitutions per site per year without “Tumba”). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail. Interpretation: Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures. Funding: Defense Biological Product Assurance Office.",
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T1 - 2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo

T2 - a retrospective genomic characterisation

AU - Mbala-Kingebeni, Placide

AU - Pratt, Catherine B.

AU - Wiley, Michael R

AU - Diagne, Moussa M.

AU - Makiala-Mandanda, Sheila

AU - Aziza, Amuri

AU - Di Paola, Nicholas

AU - Chitty, Joseph A.

AU - Diop, Mamadou

AU - Ayouba, Ahidjo

AU - Vidal, Nicole

AU - Faye, Ousmane

AU - Faye, Oumar

AU - Karhemere, Stormy

AU - Aruna, Aaron

AU - Nsio, Justus

AU - Mulangu, Felix

AU - Mukadi, Daniel

AU - Mukadi, Patrick

AU - Kombe, John

AU - Mulumba, Anastasie

AU - Duraffour, Sophie

AU - Likofata, Jacques

AU - Pukuta, Elisabeth

AU - Caviness, Katie

AU - Bartlett, Maggie L.

AU - Gonzalez, Jeanette

AU - Minogue, Timothy

AU - Sozhamannan, Shanmuga

AU - Gross, Stephen M.

AU - Schroth, Gary P.

AU - Kuhn, Jens H.

AU - Donaldson, Eric F.

AU - Delaporte, Eric

AU - Sanchez-Lockhart, Mariano

AU - Peeters, Martine

AU - Muyembe-Tamfum, Jean Jacques

AU - Alpha Sall, Amadou

AU - Palacios, Gustavo

AU - Ahuka-Mundeke, Steve

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Background: The 2018 Ebola virus disease (EVD)outbreak in Équateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures). Methods: We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 Équateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp. Findings: A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name “Tumba”. This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10−3 substitutions per site per year with “Tumba” vs 1·06 × 10−3 substitutions per site per year without “Tumba”). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail. Interpretation: Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures. Funding: Defense Biological Product Assurance Office.

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