Randomized Trial of Vaccines for Zaire Ebola Virus Disease.

BACKGROUND: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease. METHODS: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4. RESULTS: A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14. CONCLUSIONS: No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.).

Nipah Virus Infection Generates Ordered Structures in Cellulo.

Nipah virus (NiV) is a zoonotic paramyxovirus with a fatality rate of up to 92% in humans. While several pathogenic mechanisms used by NiV to counteract host immune defense responses have been described, all of the processes that take place in cells during infection are not fully characterized. Here, we describe the formation of ordered intracellular structures during NiV infection. We observed that these structures are formed specifically during NiV infection, but not with other viruses from the same Mononegavirales order (namely Ebola virus) or from other orders such as Bunyavirales (Junín virus). We also determined the kinetics of the appearance of these structures and their cellular localization at the cellular periphery. Finally, we confirmed the presence of these NiV-specific ordered structures using structured illumination microscopy (SIM), as well as their localization by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and correlative light and electron microscopy (CLEM). Herein, we describe a cytopathogenic mechanism that provides a new insight into NiV biology. These newly described ordered structures could provide a target for novel antiviral approaches.

Ebola: uma ameaça à Saúde Pública e à fauna silvestre / Ebola: a threat to public health and wildlife

Este artigo de revisão sumariza conhecimentos sobre a sintomatologia, patogenia, fatores epidemiológicos para algumas espécies da fauna silvestre acometidas pela virose, lista espécies silvestres vulneráveis à doença do vírus Ebola (EVD) e espécies de animais domésticos não vulveráveis, evidencia o uso de modelos animais para estudos objetivando a defesa de humanos e de animais contra essa doença e destaca a ameaça à saúde dos animais silvestres representada pela EVD.(AU)

This review article summarizes knowledge about the symptomatology, pathogenesis, epidemiological factors for some wildlife species affected by the virus, lists wild species vulnerable to Ebola virus disease (EVD) and non-vulverable species of domestic animals, highlights the use of animal models for studies aimed at the defense of humans and animals against this disease and highlights the threat to the health of wild animals represented by the EVD.(AU)

Strategies in Medicinal Chemistry to Discover New Hit Compounds against Ebola Virus: Challenges and Perspectives in Drug Discovery.

Ebola Virus (EBOV) is an infectious disease that mainly affects the cardiovascular system. It belongs to the Filoviridae family, consisting of filamentous envelopes and non-segmented negative RNA genome. EBOV was initially identified in Sudan and Zaire (now named the Democratic Republic of Congo) around 1967. It is transmitted mainly by contact with secretions (blood, sweat, saliva, and tears) from infected wild animals, such as non-human primates and bats. It has gained more prominence in recent years due to the recent EBOV outbreaks that occurred from 2013 to 2016, resulting in approximately 28,000 infected individuals, with a mortality rate of 40- 70%, affecting mainly Liberia, Guinea, and Sierra Leone. Despite these alarming levels, there is still no FDA-approved drug for the effective treatment of these diseases. The most advanced drug to treat EBOV is remdesivir. However, it is a high-cost drug and is available only for intravenous use. In this sense, more investments are needed in the research focused on the development of new antiviral drugs. In this context, medicinal chemistry strategies have been improving and increasingly discovering new hits that can be used in the future as a treatment against these diseases. Thus, this review will address the main advances in medicinal chemistry, such as drug discovery through computational techniques (virtual screening and virtual high throughput screening), drug repurposing, phenotypic screening assays, and employing classical medicinal chemistry, such as bioisosterism, metabolism-based drug design, and the discovery of new inhibitors through natural products, thereby presenting several promising compounds that may contain the advance of these pathogens.

Rapid diagnostic tests versus RT­PCR for Ebola virus infections: a systematic review and meta-analysis

Objective To evaluate the clinical accuracy of rapid diagnostic tests for the detection of Ebola virus. Methods We searched MEDLINE®, Embase® and Web of Science for articles published between 1976 and October 2021 reporting on clinical studies assessing the performance of Ebola virus rapid diagnostic tests compared with reverse transcription polymerase chain reaction (RT­PCR). We assessed study quality using the QUADAS-2 criteria. To estimate the pooled sensitivity and specificity of these rapid diagnostic tests, we used a bivariate random-effects meta-analysis. Findings Our search identified 113 unique studies, of which nine met the inclusion criteria. The studies were conducted in the Democratic Republic of the Congo, Guinea, Liberia and Sierra Leone and they evaluated 12 rapid diagnostic tests. We included eight studies in the meta-analysis. The pooled sensitivity and specificity of the rapid tests were 86% (95% confidence interval, CI: 80­91) and 95% (95% CI: 91­97), respectively. However, pooled sensitivity decreased to 83% (95% CI: 77­88) after removing outliers. Pooled sensitivity increased to 90% (95% CI: 82­94) when analysis was restricted to studies using the RT­PCR from altona Diagnostics as gold standard. Pooled sensitivity increased to 99% (95% CI: 67­100) when the analysis was restricted to studies using whole or capillary blood specimens. Conclusion The included rapid diagnostic tests did not detect all the Ebola virus disease cases. While the sensitivity and specificity of these tests are moderate, they are still valuable tools, especially useful for triage and detecting Ebola virus in remote areas.

On the effectiveness of communication strategies as non-pharmaceutical interventions to tackle epidemics.

When pharmaceutical interventions are unavailable to deal with an epidemic outbreak, adequate management of communication strategies can be key to reduce the contagion risks. On the one hand, accessibility to trustworthy and timely information, whilst on the other, the adoption of preventive behaviors may be both crucial. However, despite the abundance of communication strategies, their effectiveness has been scarcely evaluated or merely circumscribed to the scrutiny of public affairs. To study the influence of communication strategies on the spreading dynamics of an infectious disease, we implemented a susceptible-exposed-infected-removed-dead (SEIRD) epidemiological model, using an agent-based approach. Agents in our systems can obtain information modulating their behavior from two sources: (i) through the local interaction with other neighboring agents and, (ii) from a central entity delivering information with a certain periodicity. In doing so, we highlight how global information delivered from a central entity can reduce the impact of an infectious disease and how informing even a small fraction of the population has a remarkable impact, when compared to not informing the population at all. Moreover, having a scheme of delivering daily messages makes a stark difference on the reduction of cases, compared to the other evaluated strategies, denoting that daily delivery of information produces the largest decrease in the number of cases. Furthermore, when the information spreading relies only on local interactions between agents, and no central entity takes actions along the dynamics, then the epidemic spreading is virtually independent of the initial amount of informed agents. On top of that, we found that local communication plays an important role in an intermediate regime where information coming from a central entity is scarce. As a whole, our results highlight the importance of proper communication strategies, both accurate and daily, to tackle epidemic outbreaks.

Ebola virus disease: An emerging and re-emerging viral threat.

The genus Ebolavirus from the family Filoviridae is composed of five species including Sudan ebolavirus, Reston ebolavirus, Bundibugyo ebolavirus, Taï Forest ebolavirus, and Ebola virus (previously known as Zaire ebolavirus). These viruses have a large non-segmented, negative-strand RNA of approximately 19 kb that encodes for glycoproteins (i.e., GP, sGP, ssGP), nucleoproteins, virion proteins (i.e., VP 24, 30,40) and an RNA dependent RNA polymerase. These viruses have become a global health concern because of mortality, their rapid dissemination, new outbreaks in West-Africa, and the emergence of a new condition known as "Post-Ebola virus disease syndrome" that resembles inflammatory and autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis with uveitis. However, there are many gaps in the understanding of the mechanisms that may induce the development of such autoimmune-like syndromes. Some of these mechanisms may include a high formation of neutrophil extracellular traps, an uncontrolled "cytokine storm", and the possible formation of auto-antibodies. The likely appearance of autoimmune phenomena in Ebola survivors suppose a new challenge in the management and control of this disease and opens a new field of research in a special subgroup of patients. Herein, the molecular biology, pathogenesis, clinical manifestations, and treatment of Ebola virus disease are reviewed and some strategies for control of disease are discussed.

An evolutionary insight into emerging Ebolavirus strains isolated in Africa.

On July 19, 2019, the World Health Organization declared the current Ebolavirus (EBOV) outbreak in Congo Democratic Republic (COD) a public health emergency of international concern. To address the potential threat of EBOV evolution outpacing antibody treatment and vaccine efforts, a detailed evolutionary analysis of EBOV strains circulating in different African countries was performed. Genome composition of EBOV strains was studied using multivariate statistical analysis. To investigate the patterns of evolution of EBOV strains, a Bayesian Markov Chain Monte Carlo approach was used. Two different genetic lineages, with a distinct genome composition gave rise to the recent EBOV outbreaks in central and western Africa. Strains isolated in COD in 2018 fall into two different genetic clusters, according to their geographical location of isolation. Different amino acid substitutions among strains from these two clusters have been found, particularly in NP, GP, and L proteins. Significant differences in codon and amino acid usage among clusters were found. Strains isolated in COD in 2018 belong to two distinct genetic clusters, with distinct codon and amino acid usage. Geographical diversity plays an important role in shaping the molecular evolution of EBOV populations.

In Silico Studies against Viral Sexually Transmitted Diseases.

Sexually Transmitted Diseases (STDs) refer to a variety of clinical syndromes and infections caused by pathogens that can be acquired and transmitted through sexual activity. Among STDs widely reported in the literature, viral sexual diseases have been increasing in a number of cases globally. This emphasizes the need for prevention and treatment. Among the methods widely used in drug planning are Computer-Aided Drug Design (CADD) studies and molecular docking which have the objective of investigating molecular interactions between two molecules to better understand the three -dimensional structural characteristics of the compounds. This review will discuss molecular docking studies applied to viral STDs, such as Ebola virus, Herpes virus and HIV, and reveal promising new drug candidates with high levels of specificity to their respective targets.

Caracterización clínico epidemiológica de pacientes con ébola en un centro de tratamiento de Sierra Leona / Clinical-epidemiological characterization of Ebola disease in patients at a treatment center in Sierra Leone

Introducción: La enfermedad del ébola se dio a conocer por primera vez en 1976, con una letalidad muy elevada en todos los brotes detectados. Objetivo: Caracterizar clínica y epidemiológicamente a los pacientes portadores de la enfermedad por el virus del Ébola. Métodos: Se realizó un estudio observacional, descriptivo y transversal en 424 pacientes ingresados en un centro de tratamiento de ébola en la República de Sierra Leona, África occidental, con el diagnóstico confirmado mediante la técnica de reacción en cadena de la polimerasa para virus Ébola, durante el período de noviembre de 2014 hasta marzo de 2015. Resultados: Se muestra que el grupo etario más afectado fue el de 25 a 34 con un 25,9 por ciento. La mayor letalidad se presentó en los pacientes con más de 65 años de edad con un 44,4 por ciento. El síntoma que prevaleció fue la fiebre para un 61,8 por ciento, y el hipo se presentó en el 88,8 por ciento de los fallecidos. Conclusión: Se concluye que la enfermedad no tuvo distinción significativa con el sexo. La mayor letalidad se presentó en las edades geriátricas. Los síntomas más frecuentes fueron la fiebre, diarrea y el decaimiento. El hipo fue el signo que más se presentó en los pacientes que fallecieron(AU)

Introduction: Ebola disease was first reported in 1976 with a very high lethality in all outbreaks. Objective: To clinically and epidemiologically characterize the patients carriers of Ebola virus disease. Methods: we conducted an observational, descriptive and cross-sectional study in 424 patients admitted to an Ebola Treatment Center in the Republic of Sierra Leone, West Africa from November 2014 to March 2015. The polymerase chain reaction technique for Ebola virus confirmed the diagnosis. Medical records provided all data. Results: The age group most affected was 25 to 34 (25.9 percent). The highest lethality occurred in those over 65 years of age (44.4 percent ). Fever was the prevailing symptom (61.8 percent) and hiccups occurred in 88.8 percent of the deceased. Conclusion: Clinical manifestations were variable, although fever was the main symptom. Hiccup was a sign of poor prognosis when associated with a higher percentage of mortality. Lethality was high(AU)

Influencia de los procederes de enfermería en la sobrevivencia de los pacientes afectados por el Ébola / Influence of Nursing Procedures in the Survival of Patients Affected by Ebola

Introducción: El virus del Ébola causa una enfermedad grave sumamente infecciosa, que lleva rápidamente a la muerte, con una tasa de letalidad de hasta 90 por ciento, pero puede prevenirse. Objetivo: Describir relevancia de los procederes de enfermería en la sobrevivencia de los pacientes afectados por el Ébola Métodos: Estudio descriptivo, de corte transversal en Liberia, África Occidental, en el periodo de noviembre 2014 a febrero 2015. El universo estuvo constituido por 203 pacientes a quienes se les aplicó procederes de enfermería por enfermeros que integraron la brigada médica cubana. La información se obtuvo de la observación directa y la revisión de la base de datos estadística de la misión cubana en Liberia, se procesó mediante el Sistema SPSSS versión 11,5 a través de técnicas de estadística descriptiva. Resultados: Predominó el sexo masculino (55,66 por ciento), diciembre fue el mes de mayor ingreso (36,45 por ciento), la mayoría de los pacientes fueron ingresados en la salas de sospechosos (60,09 por ciento), predominó la administración de medicamentos por vía oral, con 820 procederes (52,59 por ciento), se logró que 51,25 por ciento de los pacientes atendidos egresaran vivos, siendo el mes de enero el de mayor letalidad (66,70 por ciento). Conclusiones: La labor realizada por los enfermeros cubanos en la lucha contra el Ébola en Liberia, África Occidental, y el cumplimiento estricto de los protocolos según procederes de enfermería contribuyó al control hemodinámico de los pacientes atendidos y a la disminución paulatina de la epidemia, así como la letalidad por dicho evento(AU)

Introduction: Ebola virus causes a highly infectious and serious disease, which quickly leads to death, with a death rate of up to 90 percent, but it can be prevented. Objective: To describe the relevance of nursing procedures in the survival of patients affected by Ebola. Methods: Descriptive, cross-sectional study carried out in West Africa, Liberia in the period from November 2014 to February 2015. The study population consisted of 203 patients who were applied nursing procedures by personnel who were part of the Cuban medical brigade. The information was obtained by direct observation and review of the statistical database of the Cuban mission in Liberia; and processed through the system SPSSS version 11.5, through descriptive statistics techniques. Results: The male sex predominated (55.66 percent). December was the month with highest admittance (36.45 percent); the majority of patients were admitted to the ward of suspects (60.09 percent). The administration of oral medications predominated, with 820 procedures (52.59 percent). It was achieved for 51.25 percent of the patients attended to be discharged alive, the month of January accounting for the highest mortality (66.70 percent). Conclusions: The work carried out by the Cuban nurses in the fight against Ebola in West Africa, Liberia and the strict compliance with the protocols according to nursing procedures contributed to the hemodynamic control of the patients attended and the gradual reduction of the epidemic, as well as the mortality for the event(AU)

Cuban Strategy and Medical Cooperation to Combat Ebola, 2014-2016.

The Ebola virus is a pathogen that causes high morbidity and mortality in epidemic events during which health personnel are frequently infected. Such an epidemic occurred in West Africa, prompting WHO to issue a call in 2014 for health personnel to be dispatched to affected countries. Cuba responded and signed an assistance agreement under which 265 Cuban health professionals, members of the Henry Reeve Emergency Medical Contingent, volunteered their services in the Republic of Guinea, Sierra Leone and Liberia. This article presents Cuba's strategy of medical aid and organization of the three medical teams formed; refers to the teams' contribution to epidemic control in treatment centers where they worked alongside other personnel; and describes measures taken in Cuba to prevent the virus from entering the country through returning volunteers or other means. In the centers where Cuban medical teams worked with other health professionals in West Africa, case fatality decreased from 80%-90% to 24%, contributing to control of the epidemic; no Ebola outbreaks occurred in Cuba. During the epidemic, two Cuban health professionals died of malaria and one physician fell ill with Ebola. This paper includes an overview of the treatment and evolution of the latter case, a doctor who contracted the disease in Sierra Leone and was treated in Geneva and Havana. KEYWORDS Ebola virus, treatment, strategy, followup, medical collaboration, Republic of Guinea, Sierra Leone, Liberia, Cuba.

Male Ebola Survivors: Do Not Forget to Use a Condom!

The current Ebola outbreak is the largest, longest, and most complex the world has ever seen, that is, the United Nations declared it "a threat to peace and security"1 and the World Health Organization acknowledged it to be a Public Health Emergency of International Concern. As new evidence emerges2 to enlighten the clinical characteristics and the prognosis of the acute phase of the disease, there is relatively scarce information about the convalescent phase, especially the measures to control the sexual transmission of Ebola.In order to assess the evidence that underlies the current recommendation (use of condom for 3 months in convalescent male3), we performed a systematic search of the literature (for articles indexed in Medline and Embase) using the following MESH terms (Ebolavirus; Hemorrhagic Fever, Ebola; Semen) with no further restrictions (Table 1).

Memorias de un enfermero cubano cara a cara con el Ébola en Guinea Conakry / Memories of a Cuban Nurse face to face with Ebola in Guinea Conakry

Introducción: La enfermedad ocasionada por el virus Ébola ha sido la peor epidemia en África Occidental entre 2014 y 2015, se infectaron más de 27 000 personas, con más de 11 000 muertes en Guinea, Liberia y Sierra Leona. Cuba fue de los primeros países del mun do en dar respuesta al llamado de la Organización Mundial de la Salud y la Organización de Naciones Unidas para enfrentar la epidemia en los países afectados, enviando 256 profesionales Médicos y Enfermeros del Contingente Internacional "Henry Reeve". Objetivo: Exponer la experiencia de un enfermero cubano en el enfrentamiento de la epidemia del virus Ébola en África Occidental. Métodos: La investigación se realizó desde una perspectiva cualitativa, a fin de poner exponer las experiencias vividas por los colaboradores de la Brigada Médica Cubana "Henry Reeve" que enfrentaron la epidemia de Ébola en Guinea Conakry desde octubre de 2014 hasta mayo de 2015. Conclusiones: Los colaboradores regresaron con la satisfacción del deber cumplido, con cero casos confirmados de Ébola en el Centro de tratamiento y en la prefectura de Coyah, se concluyó la misión con una evaluación satisfactoria(AU)

Introduction: The Ebola virus disease has been the worst epidemic in West Africa between 2014 and 2015, more than 27 000 people were infected, with more than 11 000 deaths in Guinea, Liberia and Sierra Leone. Cuba was one of the first countries worldwide to respond to the call of the World Health Organization and the United Nations to confront the epidemic in the affected countries, sending 256 medical professionals and nurses of Henry Reeve International Contingent. Objective: To present a Cuban nurse's experience in confronting the Ebola virus epidemic in West Africa. Methods: The research was conducted from a qualitative perspective, in order to expose the experiences lived by the collaborators of Henry Reeve Cuban Medical Brigade, who confronted the Ebola epidemic in Guinea Conakry from October 2014 to May 2015. Conclusions: The collaborators returned with the satisfaction of the duty fulfilled, with zero confirmed cases of Ebola in the Treatment Center and in the Coyah prefecture; the mission was concluded with a satisfactory evaluation(AU)

On the Regularities of the Polar Profiles of Proteins Related to Ebola Virus Infection and their Functional Domains.

The number of fatalities and economic losses caused by the Ebola virus infection across the planet culminated in the havoc that occurred between August and November 2014. However, little is known about the molecular protein profile of this devastating virus. This work represents a thorough bioinformatics analysis of the regularities of charge distribution (polar profiles) in two groups of proteins and their functional domains associated with Ebola virus disease: Ebola virus proteins and Human proteins interacting with Ebola virus. Our analysis reveals that a fragment exists in each of these proteins-one named the "functional domain"-with the polar profile similar to the polar profile of the protein that contains it. Each protein is formed by a group of short sub-sequences, where each fragment has a different and distinctive polar profile and where the polar profile between adjacent short sub-sequences changes orderly and gradually to coincide with the polar profile of the whole protein. When using the charge distribution as a metric, it was observed that it effectively discriminates the proteins from their functional domains. As a counterexample, the same test was applied to a set of synthetic proteins built for that purpose, revealing that any of the regularities reported here for the Ebola virus proteins and human proteins interacting with Ebola virus were not present in the synthetic proteins. Our results indicate that the polar profile of each protein studied and its corresponding functional domain are similar. Thus, when building each protein from its functional domai-adding one amino acid at a time and plotting each time its polar profile-it was observed that the resulting graphs can be divided into groups with similar polar profiles.

Cooperative RNA Recognition by a Viral Transcription Antiterminator.

RNA transcription of mononegavirales decreases gradually from the 3' leader promoter toward the 5' end of the genome, due to a decay in polymerase processivity. In the respiratory syncytial virus and metapneumovirus, the M2-1 protein ensures transcription anti-termination. Despite being a homotetramer, respiratory syncytial virus M2-1 binds two molecules of RNA of 13mer or longer per tetramer, and temperature-sensitive secondary structure in the RNA ligand is unfolded by stoichiometric interaction with M2-1. Fine quantitative analysis shows positive cooperativity, indicative of conformational asymmetry in the tetramer. RNA binds to M2-1 through a fast bimolecular association followed by slow rearrangements corresponding to an induced-fit mechanism, providing a sequential description of the time events of cooperativity. The first binding event of half of the RNA molecule to one of the sites increases the affinity of the second binding event on the adjacent contacting protomer by 15-fold, product of increased effective concentration caused by the entropic link. This mechanism allows for high-affinity binding with an otherwise relaxed sequence specificity, and instead suggests a yet undefined structural recognition signature in the RNA for modulating gene transcription. This work provides a basis for an essential event for understanding transcription antitermination in pneumoviruses and its counterpart Ebola virus VP30.

La ética de los diseños y métodos alternativos de ensayos clínicos. Una reflexión sobre el Foro Global de Bioética en Investigación del 2017

La reunión anual del Foro Global de Bioética en Investigación (GFBR, por sus siglas en inglés) se llevó a cabo en Bangkok, Tailandia, el 28 y 29 de noviembre 2017 y trató sobre la ética de los diseños y métodos alternativos de ensayos clínicos en países de bajos y medianos ingresos. En esta reunión se discutieron otras formas de generar evidencias tales como los ensayos aleatorizados por conglomerado (cluster randomized trials), que consisten en la asignación al azar de grupos en lugar de individuos independientes a una intervención, aquellos en los cuales una intervención se agrega a los conglomerados de manera escalonada (stepped wedge); los ensayos con plataformas adaptativas (adaptative platforms), que permiten modificaciones al ensayo o procedimientos estadísticos del ensayo después de su inicio, sin menoscabar su validez e integridad; y los modelos con infecciones controladas en seres humanos (controlled human infection models o CHIM)...

Enfermedad por el virus Ébola medidas de bioseguridad / Ebola virus disease biosafety measures

Resumen El virus Ébola representa el patógeno prototipo de fiebre hemorrágica viral, causando una enfermedad severa de alta tasa de mortalidad. Esta alta mortalidad, combinada con la ausencia de vacunación y de un tratamiento específico, hace que el virus Ébola sea un patógeno importante para la salud pública. La fiebre hemorrágica de Ébola se cree es una zoonosis con persistencia del virus en especies de reservorios encontrados en áreas endémicas. A pesar de todos los esfuerzos realizados en cada brote para identificar los reservorios naturales no se conocen huéspedes potenciales ni los artrópodos vectores. El manejo de los casos está basado en el aislamiento de los pacientes y en el uso de barreras de aislamiento, tales como ropa e implementos de protección como respiradores. Debido a su rápida propagación la OMS declaró que la enfermedad por el virus Ébola representa una emergencia de salud pública más allá de las fronteras y exhortó a la comunidad internacional a tomar las acciones necesarias para detener la epidemia.

Abstract Ebola virus is regarded as the prototype pathogen of viral hemorrhagic fever, causing severe disease and high case fatality rates. This high fatality, combined with the absence ot treatment and vaccination options, makes Ebola virus an important public health pathogen. Ebola hemorrhagic fever is thought to be a classic zoonosis with persistence of the Ebola virus in a reservoir species generally found in endemic areas. Although much effort has been made to identify the natural reservoirs with every large outbreak of Ebola hemorrhagic fever, neither potential hosts norarthropod vectors have been identified. Case management is based on isolation of patients and use of strict barrier nursing procedures, such as protective clothing and respirators. In addition, its rapid propagation has led the Word Health Organization (WHO) to declare on August 2014 that Ebola virus disease represents a public health emergency of international concern and urged the international community to take action to stop its spread.

An immunoinformatics-derived DNA vaccine encoding human class II T cell epitopes of Ebola virus, Sudan virus, and Venezuelan equine encephalitis virus is immunogenic in HLA transgenic mice.

Immunoinformatics tools were used to predict human leukocyte antigen (HLA) class II-restricted T cell epitopes within the envelope glycoproteins and nucleocapsid proteins of Ebola virus (EBOV) and Sudan virus (SUDV) and the structural proteins of Venezuelan equine encephalitis virus (VEEV). Selected epitopes were tested for binding to soluble HLA molecules representing 5 class II alleles (DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, and DRB1*1501). All but one of the 25 tested peptides bound to at least one of the DRB1 alleles, and 4 of the peptides bound at least moderately or weakly to all 5 DRB1 alleles. Additional algorithms were used to design a single "string-of-beads" expression construct with 44 selected epitopes arranged to avoid creation of spurious junctional epitopes. Seventeen of these 44 predicted epitopes were conserved between the major histocompatibility complex (MHC) of humans and mice, allowing initial testing in mice. BALB/c mice vaccinated with the multi-epitope construct developed statistically significant cellular immune responses to EBOV, SUDV, and VEEV peptides as measured by interferon (IFN)-γ ELISpot assays. Significant levels of antibodies to VEEV, but not EBOV, were also detected in vaccinated BALB/c mice. To assess immunogenicity in the context of a human MHC, HLA-DR3 transgenic mice were vaccinated with the multi-epitope construct and boosted with a mixture of the 25 peptides used in the binding assays. The vaccinated HLA-DR3 mice developed significant cellular immune responses to 4 of the 25 (16%) tested individual class II peptides as measured by IFN-γ ELISpot assays. In addition, these mice developed antibodies against EBOV and VEEV as measured by ELISA. While a low but significant level of protection was observed in vaccinated transgenic mice after aerosol exposure to VEEV, no protection was observed after intraperitoneal challenge with mouse-adapted EBOV. These studies provide proof of concept for the use of an informatics approach to design a multi-agent, multi-epitope immunogen and provide a basis for further testing aimed at focusing immune responses toward desired protective T cell epitopes.