scholarly journals Ebolavirus: Comparison of Survivor Immunology and Animal Models in the Search for a Correlate of Protection

2021 ◽  
Vol 11 ◽  
Author(s):  
Stephanie Longet ◽  
Jack Mellors ◽  
Miles W. Carroll ◽  
Tom Tipton

Ebola viruses are enveloped, single-stranded RNA viruses belonging to the Filoviridae family and can cause Ebola virus disease (EVD), a serious haemorrhagic illness with up to 90% mortality. The disease was first detected in Zaire (currently the Democratic Republic of Congo) in 1976. Since its discovery, Ebola virus has caused sporadic outbreaks in Africa and was responsible for the largest 2013–2016 EVD epidemic in West Africa, which resulted in more than 28,600 cases and over 11,300 deaths. This epidemic strengthened international scientific efforts to contain the virus and develop therapeutics and vaccines. Immunology studies in animal models and survivors, as well as clinical trials have been crucial to understand Ebola virus pathogenesis and host immune responses, which has supported vaccine development. This review discusses the major findings that have emerged from animal models, studies in survivors and vaccine clinical trials and explains how these investigations have helped in the search for a correlate of protection.

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 439 ◽  
Author(s):  
David Brett-Major ◽  
James Lawler

After more than 28,000 Ebola virus disease cases and at least 11,000 deaths in West Africa during the 2014–2016 epidemic, the world remains without a licensed vaccine or therapeutic broadly available and demonstrated to alleviate suffering. This deficiency has been felt acutely in the two, short, following years with two Ebola virus outbreaks in the Democratic Republic of Congo (DRC), and a Marburg virus outbreak in Uganda. Despite billions of U.S. dollars invested in developing medical countermeasures for filoviruses in the antecedent decades, resulting in an array of preventative, diagnostic, and therapeutic products, none are available on commercial shelves. This paper explores why just-in-time research efforts in the field during the West Africa epidemic failed, as well as some recent initiatives to prevent similarly lost opportunities.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Amorim Tomaz ◽  
F I P M Bastos ◽  
R S Santos ◽  
M Mossoko

Abstract The world has seen outbreaks of emergency and re-emergency of infectious diseases very often in the past years, many of them with devastating consequences for low-income countries with fragile or nonexistent health system, covid-19 being by now the last of a long series of global challenges. Although it is a huge challenge for the whole world, one country is facing it together with a current Ebola outbreak plus violence and some other diseases. The Democratic Republic of Congo is facing the immediate effects of both epidemics as illness and death, however its consequences at the political and economic level are usually more complex and may be protracted. Following the debate on why poor countries remain poor, it is maybe useful to rethink poverty and inequality keeping in mind Amartya Sen's seminal concepts: development must comprise freedom and respect for human rights and institutions at the price of fostering a vicious circle of (re)emerging diseases and structural violence. Ebola epidemics, that usually face some challenges when they happen alone, now together with malaria, measles, plague and covid, on top of violence in some areas, the disease sees its protocols harmed: for covid the orientation is to stay isolated, for Ebola the response includes tracking contacts. What means coming with a team to field to do the mapping in the middle of a confinement. The surveillance for such many epidemics on top of violence and humanitarian crisis makes the Democratic Republic of Congo one of the most worrying countries in terms of consequences of the Covid outbreak. Key messages Study of the association between the Covid, Ebola virus disease outbreak and the at-risk population living in the conflict zone in Eastern Democratic Republic of Congo. The study presents the difficulties that the population encountered in the face of restrictions imposed by armed groups to reach health services during an Ebola outbreak, in a conflict zone.


Author(s):  
Justus Nsio ◽  
Jimmy Kapetshi ◽  
Sheila Makiala ◽  
Frederic Raymond ◽  
Gaston Tshapenda ◽  
...  

2019 ◽  
Vol 26 (7) ◽  
Author(s):  
Ashleigh R Tuite ◽  
Alexander G Watts ◽  
Kamran Khan ◽  
Isaac I Bogoch

Abstract Background The 2018–2019 Ebola virus disease (EVD) outbreak in North Kivu and Ituri provinces, Democratic Republic of Congo (DRC), continues to spread. The recent discovery of cases in Uganda and in Goma, a major city in the eastern DRC, raises concern for potential EVD transmission in distant locales via commercial air travel. Methods We examined air travel patterns from the affected region with itinerary-level data from the International Air Transport Association for the year 2018 between July and October, inclusive. We focused on three scenarios: (i) travel from Beni airport, (ii) travel from Beni, Goma and Bunia airports and (iii) travel from Beni, Goma and Bunia, and Kigali airports. We evaluated country-level Infectious Disease Vulnerability Index (IDVI) scores for traveller destinations. Results There were 2255 commercial air passengers departing from Beni Airport during the specified time frame, all with domestic destinations, and 55% of which were to Goma. A total of 29 777 passengers travelled from Beni, Bunia and Goma airports during this time frame, with most travel (94.6%) departing from Goma Airport. A total of 72.4% of passengers’ final destination from these three airports were within the DRC, primarily to Kinshasa. There were 166 281 outbound passengers from Beni, Bunia, Goma and Kigali airports with the majority (82.1%) of passengers departing from Kigali. The most frequent destinations from these airports were Nairobi, Kinshasa and Entebbe. Eight of the 10 destinations with greatest passenger volumes are to countries with IDVI scores less than 0.4. Conclusion There is little commercial airline connectivity from the current EVD-affected area; however, larger cities in DRC and throughout East Africa should be aware of the low potential for EVD importation through this route. Most countries at greatest risk for EVD importation have limited capacity to manage these cases.


2021 ◽  
Vol 11 ◽  
Author(s):  
Anahita Fathi ◽  
Marylyn M. Addo ◽  
Christine Dahlke

Vaccines are one of the greatest public health achievements and have saved millions of lives. They represent a key countermeasure to limit epidemics caused by emerging infectious diseases. The Ebola virus disease crisis in West Africa dramatically revealed the need for a rapid and strategic development of vaccines to effectively control outbreaks. Seven years later, in light of the SARS-CoV-2 pandemic, this need has never been as urgent as it is today. Vaccine development and implementation of clinical trials have been greatly accelerated, but still lack strategic design and evaluation. Responses to vaccination can vary widely across individuals based on factors like age, microbiome, co-morbidities and sex. The latter aspect has received more and more attention in recent years and a growing body of data provide evidence that sex-specific effects may lead to different outcomes of vaccine safety and efficacy. As these differences might have a significant impact on the resulting optimal vaccine regimen, sex-based differences should already be considered and investigated in pre-clinical and clinical trials. In this Review, we will highlight the clinical observations of sex-specific differences in response to vaccination, delineate sex differences in immune mechanisms, and will discuss the possible resulting implications for development of vaccine candidates against emerging infections. As multiple vaccine candidates against COVID-19 that target the same antigen are tested, vaccine development may undergo a decisive change, since we now have the opportunity to better understand mechanisms that influence vaccine-induced reactogenicity and effectiveness of different vaccines.


2018 ◽  
Author(s):  
Lee Worden ◽  
Rae Wannier ◽  
Nicole A. Hoff ◽  
Kamy Musene ◽  
Bernice Selo ◽  
...  

AbstractBackgroundAs of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak with case-count time series from prior outbreaks to project the short-term and long-term course of the outbreak.MethodsFor short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott’s rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts.ResultsDuring validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872–1054) and 955 cases by March 4 (95% prediction interval: 874–1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876–933) and 898 (95% prediction interval: 877–983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013–2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone.ConclusionsOur projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.Author summaryAs of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has been reported, and in which EVD cases and their contacts have been difficult for health workers to reach. We used an ensemble of models to estimate EVD transmission rates and to forecast the short- and long-term course of the outbreak. Our models project that a final size of roughly up to 300 additional cases is most likely, and estimate that transmission rates are higher than would be seen under optimal levels of contact tracing and vaccination. While a catastrophic outbreak is not projected, is it not ruled out, and prevention and vigilance are warranted.


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