scholarly journals Initiating a watch list for Ebola virus antibody escape mutations

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1674 ◽  
Author(s):  
Craig R. Miller ◽  
Erin L. Johnson ◽  
Aran Z. Burke ◽  
Kyle P. Martin ◽  
Tanya A. Miura ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
West Africa ◽  
Experimental Research ◽  
Envelope Glycoprotein ◽  
Ebola Virus ◽  
Virus Antibody ◽  
Viral Pathogens ◽  
Evolutionary Response ◽  
Modeling Interactions ◽  
Watch List

The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.

scholarly journals Expanding the watch list for potential Ebola virus antibody escape mutations

2019 ◽  
Author(s):  
Jagdish Suresh Patel ◽  
Caleb J. Quates ◽  
Erin L. Johnson ◽  
F. Marty Ytreberg
Keyword(s):  
Ebola Virus ◽  
Democratic Republic ◽  
Disease Outbreak ◽  
Virus Antibody ◽  
Antibody Treatment ◽  
Single Strain ◽  
Western Africa ◽  
Evolutionary Response ◽  
Republic Of The Congo ◽  
Watch List

The 2014 outbreak of Ebola virus (EBOV) in Western Africa is the largest recorded filovirus disease outbreak and lead to the death of over 11,000 people. This deadly virus still poses a grave epidemic threat as evidenced by the current (since May 2018) EBOV outbreak in the Democratic Republic of the Congo which has already claimed the lives of over 250 people. One important strategy for combating EBOV epidemics is to anticipate how the evolution of EBOV might undermine treatment since the development of vaccines and antibody therapies are typically based on a single strain (often the 1976 Mayinga) of the EBOV envelope glycoprotein (GP). In a previous study we initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between EBOV GP and the monoclonal antibody KZ52. This watch list was generated using molecular modeling to estimate the effect of every possible mutation of GP. The final watch list containing 34 mutations were predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. In this study, we expand our watch list by including three more monoclonal antibodies with distinct epitopes on GP, namely Antibody 100 (Ab100), Antibody 114 (Ab114) and 13F6-1-2. Our updated watch list contains 127 mutations, three of which have been seen in humans or are experimentally associated with reduced efficacy of antibody treatment. We believe mutations on this broad watch list require attention since they may be a signal of an evolutionary response from EBOV to treatment that could diminish the effectiveness of interventions.

scholarly journals Expanding the watch list for potential Ebola virus antibody escape mutations

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0211093 ◽  
Author(s):  
Jagdish Suresh Patel ◽  
Caleb J. Quates ◽  
Erin L. Johnson ◽  
F. Marty Ytreberg
Keyword(s):  
Ebola Virus ◽  
Virus Antibody ◽  
Watch List

scholarly journals Characterisation of the T-cell response to Ebola virus glycoprotein amongst survivors of the 2013–16 West Africa epidemic

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
T. R. W. Tipton ◽  
Y. Hall ◽  
J. A. Bore ◽  
A. White ◽  
L. S. Sibley ◽  
...  
Keyword(s):  
T Cell ◽  
West Africa ◽  
Cell Response ◽  
Ebola Virus ◽  
Medical Condition ◽  
Virus Disease ◽  
T Cell Response ◽  
Ebola Virus Disease ◽  
Cell Phenotype ◽  
T Cell Epitopes

AbstractZaireebolavirus (EBOV) is a highly pathogenic filovirus which can result in Ebola virus disease (EVD); a serious medical condition that presents as flu like symptoms but then often leads to more serious or fatal outcomes. The 2013–16 West Africa epidemic saw an unparalleled number of cases. Here we show characterisation and identification of T cell epitopes in surviving patients from Guinea to the EBOV glycoprotein. We perform interferon gamma (IFNγ) ELISpot using a glycoprotein peptide library to identify T cell epitopes and determine the CD4+ or CD8+ T cell component response. Additionally, we generate data on the T cell phenotype and measure polyfunctional cytokine secretion by these antigen specific cells. We show candidate peptides able to elicit a T cell response in EBOV survivors and provide inferred human leukocyte antigen (HLA) allele restriction. This data informs on the long-term T cell response to Ebola virus disease and highlights potentially important immunodominant peptides.

scholarly journals COVID-19 in West Africa: regional resource mobilisation and allocation in the first year of the pandemic

2021 ◽  
Vol 6 (5) ◽  
pp. e004762
Author(s):  
Césaire Ahanhanzo ◽  
Ermel Ameswue Kpogbe Johnson ◽  
Ejemai Amaize Eboreime ◽  
Sombié Issiaka ◽  
Ben Idrissa Traoré ◽  
...  
Keyword(s):  
West Africa ◽  
Ebola Virus ◽  
Virus Disease ◽  
First Year ◽  
African Countries ◽  
Response Strategies ◽  
African Health ◽  
The Usa ◽  
Health Organization ◽  
Resource Mobilisation

The world continues to battle the ongoing COVID-19 pandemic. Whereas many countries are currently experiencing the second wave of the outbreak; Africa, despite being the last continent to be affected by the virus, has not experienced as much devastation as other continents. For example, West Africa, with a population of 367 million people, had confirmed 412 178 cases of COVID-19 with 5363 deaths as of 14 March 2021; compared with the USA which had recorded almost 30 million cases and 530 000 deaths, despite having a slightly smaller population (328 million). Several postulations have been made in an attempt to explain this phenomenon. One hypothesis is that African countries have leveraged on experiences from past epidemics to build resilience and response strategies which may be contributing to protecting the continent’s health systems from being overwhelmed. This practice paper from the West African Health Organization presents experience and data from the field on how countries in the region mobilised support to address the pandemic in the first year, leveraging on systems, infrastructure, capacities developed and experiences from the 2014 Ebola virus disease outbreak.

scholarly journals Ebola Virus Epidemic in West Africa: Global Health Economic Challenges, Lessons Learned, and Policy Recommendations

2017 ◽  
Vol 13 ◽  
pp. 67-70 ◽  
Author(s):  
Mahmoud Elmahdawy ◽  
Gihan H. Elsisi ◽  
Joao Carapinha ◽  
Mohamed Lamorde ◽  
Abdulrazaq Habib ◽  
...  
Keyword(s):  
Health Economic ◽  
Global Health ◽  
West Africa ◽  
Ebola Virus ◽  
Lessons Learned ◽  
Policy Recommendations
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