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1.
Cell ; 184(8): 1960-1961, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33831378

RESUMEN

The events of the past year have underscored the serious and rapid threat that emerging viruses pose to global health. However, much of the rapid progress in understanding and combating SARS-CoV-2 was made possible because of the decades of important groundwork laid from researchers studying other emergent infectious diseases. The 2021 John Dirks Canada Gairdner Global Health award recognizes the contributions of Joseph Sriyal Malik Peiris and Yi Guan toward understanding the origins and options for control of newly emerging infectious disease outbreaks in Asia, notably zoonotic influenza and severe acute respiratory syndrome (SARS). Cell's Nicole Neuman corresponded with Yi Guan about his path to becoming a viral infection sleuth and the challenges of understanding emerging pathogens and their origins. Excerpts of their exchange are included here.


Asunto(s)
Enfermedades Transmisibles Emergentes , Brotes de Enfermedades , Gripe Humana , Zoonosis , Animales , Asia , /transmisión , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/historia , Enfermedades Transmisibles Emergentes/transmisión , Brotes de Enfermedades/historia , Salud Global , Historia del Siglo XXI , Humanos , Gripe Humana/epidemiología , Gripe Humana/historia , Gripe Humana/transmisión , Zoonosis/epidemiología , Zoonosis/transmisión
2.
Nat Med ; 27(4): 591-600, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33846611

RESUMEN

Examination of the vaccine strategies and technical platforms used for the COVID-19 pandemic in the context of those used for previous emerging and reemerging infectious diseases and pandemics may offer some mutually beneficial lessons. The unprecedented scale and rapidity of dissemination of recent emerging infectious diseases pose new challenges for vaccine developers, regulators, health authorities and political constituencies. Vaccine manufacturing and distribution are complex and challenging. While speed is essential, clinical development to emergency use authorization and licensure, pharmacovigilance of vaccine safety and surveillance of virus variants are also critical. Access to vaccines and vaccination needs to be prioritized in low- and middle-income countries. The combination of these factors will weigh heavily on the ultimate success of efforts to bring the current and any future emerging infectious disease pandemics to a close.


Asunto(s)
/inmunología , Enfermedades Transmisibles Emergentes/prevención & control , Vacunas/inmunología , Vacunas contra el Cólera/inmunología , Enfermedades Transmisibles Emergentes/epidemiología , Vacunas contra el Dengue/inmunología , Accesibilidad a los Servicios de Salud , Humanos , Farmacovigilancia , Vacunas Tifoides-Paratifoides/inmunología , Vacuna contra la Fiebre Amarilla/inmunología
3.
Parasite ; 28: 35, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33835021

RESUMEN

Debates about emerging infectious diseases often oppose natural conceptions of zoonotic reservoirs with cultural practices bringing humans into contact with animals. This article compares the representations of cross-species pathogens at ontological levels below the opposition between nature and culture. It describes the perceptions of distinctions between interiority and physicality, between wild and domestic, and between sick and dead in three different contexts where human societies manage animal diseases: Australia, Laos and Mongolia. Our article also argues that zoonotic pathogens are one of the entities mobilized by local knowledge to attenuate troubles in ordinary relations with animals, and shows that the conservation of cultural heritage is a tool of mitigation for infectious diseases emerging in animal reservoirs.


Asunto(s)
Enfermedades de los Animales , Enfermedades Transmisibles Emergentes , Animales , Animales Salvajes , Australia , Reservorios de Enfermedades , Humanos , Zoonosis
4.
Indian J Med Res ; 153(3): 264-271, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33906988

RESUMEN

The emergence of SARS-CoV-2 and its rapid spread globally emphasizes the ever-present threat of emerging and re-emerging infectious diseases. In this review, the pathogen pyramid framework was utilized to identify the "unknown unknowns" associated with the emergence and rapid transmission of novel infectious disease agents. Given that the evolutionary origin of most of the emerging infectious disease agents can be traced to an animal source, we argue the need to integrate the "One Health" approach as a part of surveillance activities. The need for focusing on undertaking global and regional mapping activities to identify novel pathogens is discussed, given that there are an estimated 1.67 million unknown viruses, of which around 631,000 to 827,000 unknown viruses have the capacity to infect human beings. The emerging risks due to the ever-expanding interface between human, animals, both domestic and wildlife, and the environment are highlighted, these are largely driven by the need for safe habitation, growing food, developing infrastructure to support the increasing human population and desire for economic growth. The One Health approach provides a holistic way to address these cross-sectoral issues, by bridging institutional gaps, enumerating priority risk areas and pathogens, and highlighting putative risk factors for subsequent spillover events involving emerging and re-emerging infectious disease pathogens at the human-animal-environment interface.


Asunto(s)
Enfermedades Transmisibles Emergentes , Salud Única , Animales , Enfermedades Transmisibles Emergentes/epidemiología , Humanos , Zoonosis/epidemiología
6.
Proc Natl Acad Sci U S A ; 118(15)2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33822740

RESUMEN

The death toll and economic loss resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are stark reminders that we are vulnerable to zoonotic viral threats. Strategies are needed to identify and characterize animal viruses that pose the greatest risk of spillover and spread in humans and inform public health interventions. Using expert opinion and scientific evidence, we identified host, viral, and environmental risk factors contributing to zoonotic virus spillover and spread in humans. We then developed a risk ranking framework and interactive web tool, SpillOver, that estimates a risk score for wildlife-origin viruses, creating a comparative risk assessment of viruses with uncharacterized zoonotic spillover potential alongside those already known to be zoonotic. Using data from testing 509,721 samples from 74,635 animals as part of a virus discovery project and public records of virus detections around the world, we ranked the spillover potential of 887 wildlife viruses. Validating the risk assessment, the top 12 were known zoonotic viruses, including SARS-CoV-2. Several newly detected wildlife viruses ranked higher than known zoonotic viruses. Using a scientifically informed process, we capitalized on the recent wealth of virus discovery data to systematically identify and prioritize targets for investigation. The publicly accessible SpillOver platform can be used by policy makers and health scientists to inform research and public health interventions for prevention and rapid control of disease outbreaks. SpillOver is a living, interactive database that can be refined over time to continue to improve the quality and public availability of information on viral threats to human health.


Asunto(s)
Enfermedades Transmisibles Emergentes , Pandemias , Zoonosis , Animales , /transmisión , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/transmisión , Humanos , Zoonosis/epidemiología , Zoonosis/transmisión
7.
Artículo en Inglés | MEDLINE | ID: mdl-33802869

RESUMEN

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease and that is a severe threat to public health considering its high fatality and person-to-person transmission. In order to obtain an updated and deep understanding of the epidemiological characteristics of SFTS in mainland China, we used Pearson's chi-squared test to compare the fatality rate and demographic characteristics in different groups. Data were analyzed in R3.6.1 (R Development Core Team 2018), while the visualization was performed in ArcGIS 10 (ESRI, Redlands, CA, USA), and the statistical significance was set at p < 0.05. A total of 13,824 SFTS cases involving 8899 lab-confirmed cases and 4925 probable cases were reported and included in the epidemiological analysis. Our study found that the number of SFTS cases showed an increasing trend with a small decrease in the past three years. The laboratory-confirmed rate was about 64.4%, which varied between different years and areas. Although most cases (99.3%) were distributed in 7 provinces (Henan, Shandong, Anhui, Hubei, Liaoning, Zhejiang, and Jiangsu), the regional distribution of SFTS gradually expanded from 5 provinces in 2010 to 25 provinces by 2019, especially at the town level. The SFTS cases were mainly sporadic. A total of 96.5% occurred from April to October, and 93.3% of cases were concentrated in middle-aged and elderly people (40-84 years old). Farmers were the main high-risk population. Female cases were slightly more than male cases; however, there were differences between different provinces. The mortality rate showed an increasing trend with age. Overall, the SFTS cases were mainly middle-aged and elderly farmers that sporadically distributed throughout seven provinces with a spatially expanding trend. The laboratory-confirmed rate varied in different years and provinces, which implied that the diagnosis and report criteria for SFTS should be further updated and unified in order to get a better understanding of its epidemiological characteristics and provide scientific data for SFTS control.


Asunto(s)
Infecciones por Bunyaviridae , Enfermedades Transmisibles Emergentes , Phlebovirus , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Bunyaviridae/epidemiología , China/epidemiología , Ciudades , Femenino , Humanos , Masculino , Persona de Mediana Edad
8.
BMC Infect Dis ; 21(1): 265, 2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33731022

RESUMEN

BACKGROUND: Increasing arbovirus infections have been a global burden in recent decades. Many countries have experienced the periodic emergence of arbovirus diseases. However, information on the prevalence of arboviruses is largely unknown or infrequently updated because of the lack of surveillance studies, especially in Africa. METHODS: A surveillance study was conducted in Gabon, Central Africa, on arboviruses, which are a major public health concern in Africa, including: West Nile virus (WNV), dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Serological and molecular assays were performed to investigate past infection history and the current status of infection, using serum samples collected from healthy individuals and febrile patients, respectively. RESULTS: The overall seroprevalence during 2014-2017 was estimated to be 25.3% for WNV, 20.4% for DENV, 40.3% for ZIKV, 60.7% for YFV, 61.2% for CHIKV, and 14.3% for RVFV. No significant differences were found in the seroprevalence of any of the viruses between the male and female populations. However, a focus on the mean age in each arbovirus-seropositive individual showed a significantly younger age in WNV- and DENV-seropositive individuals than in CHIKV-seropositive individuals, indicating that WNV and DENV caused a relatively recent epidemic in the region, whereas CHIKV had actively circulated before. Of note, this indication was supported by the detection of both WNV and DENV genomes in serum samples collected from febrile patients after 2016. CONCLUSIONS: This study revealed the recent re-emergence of WNV and DENV in Gabon as well as the latest seroprevalence state of the major arboviruses, which indicated the different potential risks of virus infections and virus-specific circulation patterns. This information will be helpful for public health organizations and will enable a rapid response towards these arbovirus infections, thereby preventing future spread in the country.


Asunto(s)
Arbovirus/aislamiento & purificación , Dengue/epidemiología , Infección por el Virus Zika/epidemiología , Adolescente , Animales , Infecciones por Arbovirus/diagnóstico , Infecciones por Arbovirus/epidemiología , Arbovirus/clasificación , Niño , Preescolar , Enfermedades Transmisibles Emergentes , Dengue/diagnóstico , Femenino , Fiebre/epidemiología , Fiebre/virología , Gabón/epidemiología , Humanos , Lactante , Masculino , Salud Pública , Estudios Seroepidemiológicos , Infección por el Virus Zika/diagnóstico
9.
Arch Virol ; 166(5): 1455-1462, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33704558

RESUMEN

During the dengue epidemic in Yunnan Province, China, during 2019, a concurrent outbreak of chikungunya occurred in the city of Ruili, which is located in the southwest of the province, adjacent to Myanmar. As part of this outbreak, three neonatal cases of infection with indigenous chikungunya virus from mother-to-child (vertical) transmission were observed. Isolates of chikungunya virus were obtained from 37 serum samples of patients with chikungunya during this outbreak, and a phylogenetic analysis of these isolates revealed that they belong to the Indian Ocean subclade of the East/Central/South African genotype. The E1 genes of these viruses did not harbor the A226V mutation.


Asunto(s)
Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Enfermedades Transmisibles Emergentes/virología , Transmisión Vertical de Enfermedad Infecciosa , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/transmisión , Virus Chikungunya/clasificación , Virus Chikungunya/genética , China/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/transmisión , Brotes de Enfermedades , Femenino , Genoma Viral/genética , Genotipo , Humanos , Masculino , Mutación , Filogenia , ARN Viral/genética , Proteínas Virales/genética
12.
Nat Med ; 27(3): 388-395, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33723452

RESUMEN

Epidemic nowcasting broadly refers to assessing the current state by understanding key pathogenic, epidemiologic, clinical and socio-behavioral characteristics of an ongoing outbreak. Its primary objective is to provide situational awareness and inform decisions on control responses. In the event of large-scale sustained emergencies, such as the COVID-19 pandemic, scientists need to constantly update their aims and analytics with respect to the rapidly evolving emergence of new questions, data and findings in order to synthesize real-time evidence for policy decisions. In this Perspective, we share our views on the functional aims, rationale, data requirements and challenges of nowcasting at different stages of an epidemic, drawing on the ongoing COVID-19 experience. We highlight how recent advances in the computational and laboratory sciences could be harnessed to complement traditional approaches to enhance the scope, timeliness, reliability and utility of epidemic nowcasting.


Asunto(s)
/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Epidemias , Predicción/métodos , Enfermedades Transmisibles Emergentes/diagnóstico , Brotes de Enfermedades/historia , Epidemias/historia , Historia del Siglo XXI , Humanos , Pandemias , Reproducibilidad de los Resultados
13.
Nat Med ; 27(3): 401-410, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33723456

RESUMEN

The twenty-first century has already recorded more than ten major epidemic or pandemic virus emergence events, including the ongoing and devastating coronavirus disease 2019 (COVID-19) pandemic. As viral disease emergence is expected to accelerate, these data dictate a need for proactive approaches to develop broadly active family-specific and cross-family therapeutics for use in future disease outbreaks. Emphasis should focus not only on the development of broad-spectrum small-molecule and antibody direct-acting antivirals, but also on host-factor therapeutics, including repurposing previously approved or in-pipeline drugs. Another new class of therapeutics with great antiviral therapeutic potential is RNA-based therapeutics. Rather than only focusing on known risks, dedicated efforts must be made toward pre-emptive research focused on outbreak-prone virus families, ultimately offering a strategy to shorten the gap between outbreak and response. Emphasis should also focus on orally available drugs for outpatient use, if possible, and on identifying combination therapies that combat viral and immune-mediated pathologies, extend the effectiveness of therapeutic windows and reduce drug resistance. While such an undertaking will require new vision, dedicated funding and private, federal and academic partnerships, this approach offers hope that global populations need never experience future pandemics such as COVID-19.


Asunto(s)
Enfermedades Transmisibles Emergentes/terapia , Terapias en Investigación , Virosis/terapia , Antivirales/uso terapéutico , /epidemiología , Desarrollo de Medicamentos/métodos , Desarrollo de Medicamentos/tendencias , Reposicionamiento de Medicamentos , Historia del Siglo XXI , Humanos , Invenciones/tendencias , Pandemias , Terapias en Investigación/métodos , Terapias en Investigación/tendencias
14.
Cell ; 184(6): 1604-1620, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33740455

RESUMEN

Historically, emerging viruses appear constantly and have cost millions of human lives. Currently, climate change and intense globalization have created favorable conditions for viral transmission. Therefore, effective antivirals, especially those targeting the conserved protein in multiple unrelated viruses, such as the compounds targeting RNA-dependent RNA polymerase, are urgently needed to combat more emerging and re-emerging viruses in the future. Here we reviewed the development of antivirals with common targets, including those against the same protein across viruses, or the same viral function, to provide clues for development of antivirals for future epidemics.


Asunto(s)
Antivirales/uso terapéutico , Enfermedades Transmisibles Emergentes/tratamiento farmacológico , Enfermedades Transmisibles Emergentes/epidemiología , Terapia Molecular Dirigida/métodos , Pandemias , Virosis/tratamiento farmacológico , Virosis/epidemiología , Virus/enzimología , Animales , Antivirales/farmacología , Enfermedades Transmisibles Emergentes/virología , Humanos , Proteínas del Envoltorio Viral/antagonistas & inhibidores , Virosis/virología , Internalización del Virus/efectos de los fármacos
15.
Lancet Infect Dis ; 21(2): 193-202, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33729915

RESUMEN

BACKGROUND: Non-pharmaceutical interventions (NPIs) were implemented by many countries to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. A resurgence in COVID-19 cases has been reported in some countries that lifted some of these NPIs. We aimed to understand the association of introducing and lifting NPIs with the level of transmission of SARS-CoV-2, as measured by the time-varying reproduction number (R), from a broad perspective across 131 countries. METHODS: In this modelling study, we linked data on daily country-level estimates of R from the London School of Hygiene & Tropical Medicine (London, UK) with data on country-specific policies on NPIs from the Oxford COVID-19 Government Response Tracker, available between Jan 1 and July 20, 2020. We defined a phase as a time period when all NPIs remained the same, and we divided the timeline of each country into individual phases based on the status of NPIs. We calculated the R ratio as the ratio between the daily R of each phase and the R from the last day of the previous phase (ie, before the NPI status changed) as a measure of the association between NPI status and transmission of SARS-CoV-2. We then modelled the R ratio using a log-linear regression with introduction and relaxation of each NPI as independent variables for each day of the first 28 days after the change in the corresponding NPI. In an ad-hoc analysis, we estimated the effect of reintroducing multiple NPIs with the greatest effects, and in the observed sequence, to tackle the possible resurgence of SARS-CoV-2. FINDINGS: 790 phases from 131 countries were included in the analysis. A decreasing trend over time in the R ratio was found following the introduction of school closure, workplace closure, public events ban, requirements to stay at home, and internal movement limits; the reduction in R ranged from 3% to 24% on day 28 following the introduction compared with the last day before introduction, although the reduction was significant only for public events ban (R ratio 0·76, 95% CI 0·58-1·00); for all other NPIs, the upper bound of the 95% CI was above 1. An increasing trend over time in the R ratio was found following the relaxation of school closure, bans on public events, bans on public gatherings of more than ten people, requirements to stay at home, and internal movement limits; the increase in R ranged from 11% to 25% on day 28 following the relaxation compared with the last day before relaxation, although the increase was significant only for school reopening (R ratio 1·24, 95% CI 1·00-1·52) and lifting bans on public gatherings of more than ten people (1·25, 1·03-1·51); for all other NPIs, the lower bound of the 95% CI was below 1. It took a median of 8 days (IQR 6-9) following the introduction of an NPI to observe 60% of the maximum reduction in R and even longer (17 days [14-20]) following relaxation to observe 60% of the maximum increase in R. In response to a possible resurgence of COVID-19, a control strategy of banning public events and public gatherings of more than ten people was estimated to reduce R, with an R ratio of 0·71 (95% CI 0·55-0·93) on day 28, decreasing to 0·62 (0·47-0·82) on day 28 if measures to close workplaces were added, 0·58 (0·41-0·81) if measures to close workplaces and internal movement restrictions were added, and 0·48 (0·32-0·71) if measures to close workplaces, internal movement restrictions, and requirements to stay at home were added. INTERPRETATION: Individual NPIs, including school closure, workplace closure, public events ban, ban on gatherings of more than ten people, requirements to stay at home, and internal movement limits, are associated with reduced transmission of SARS-CoV-2, but the effect of introducing and lifting these NPIs is delayed by 1-3 weeks, with this delay being longer when lifting NPIs. These findings provide additional evidence that can inform policy-maker decisions on the timing of introducing and lifting different NPIs, although R should be interpreted in the context of its known limitations. FUNDING: Wellcome Trust Institutional Strategic Support Fund and Data-Driven Innovation initiative.


Asunto(s)
Número Básico de Reproducción , Modelos Teóricos , Cuarentena , /prevención & control , Enfermedades Transmisibles Emergentes/prevención & control , Salud Global , Humanos , Factores de Tiempo
16.
JMIR Public Health Surveill ; 7(3): e26719, 2021 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-33759790

RESUMEN

BACKGROUND: Patient travel history can be crucial in evaluating evolving infectious disease events. Such information can be challenging to acquire in electronic health records, as it is often available only in unstructured text. OBJECTIVE: This study aims to assess the feasibility of annotating and automatically extracting travel history mentions from unstructured clinical documents in the Department of Veterans Affairs across disparate health care facilities and among millions of patients. Information about travel exposure augments existing surveillance applications for increased preparedness in responding quickly to public health threats. METHODS: Clinical documents related to arboviral disease were annotated following selection using a semiautomated bootstrapping process. Using annotated instances as training data, models were developed to extract from unstructured clinical text any mention of affirmed travel locations outside of the continental United States. Automated text processing models were evaluated, involving machine learning and neural language models for extraction accuracy. RESULTS: Among 4584 annotated instances, 2659 (58%) contained an affirmed mention of travel history, while 347 (7.6%) were negated. Interannotator agreement resulted in a document-level Cohen kappa of 0.776. Automated text processing accuracy (F1 85.6, 95% CI 82.5-87.9) and computational burden were acceptable such that the system can provide a rapid screen for public health events. CONCLUSIONS: Automated extraction of patient travel history from clinical documents is feasible for enhanced passive surveillance public health systems. Without such a system, it would usually be necessary to manually review charts to identify recent travel or lack of travel, use an electronic health record that enforces travel history documentation, or ignore this potential source of information altogether. The development of this tool was initially motivated by emergent arboviral diseases. More recently, this system was used in the early phases of response to COVID-19 in the United States, although its utility was limited to a relatively brief window due to the rapid domestic spread of the virus. Such systems may aid future efforts to prevent and contain the spread of infectious diseases.


Asunto(s)
Enfermedades Transmisibles Emergentes/diagnóstico , Registros Electrónicos de Salud , Almacenamiento y Recuperación de la Información/métodos , Vigilancia en Salud Pública/métodos , Viaje/estadística & datos numéricos , Algoritmos , Enfermedades Transmisibles Emergentes/epidemiología , Estudios de Factibilidad , Femenino , Humanos , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Procesamiento de Lenguaje Natural , Reproducibilidad de los Resultados , Estados Unidos/epidemiología
18.
Front Immunol ; 12: 598778, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33717077

RESUMEN

Emerging infectious diseases (EIDs) caused by viruses are increasing in frequency, causing a high disease burden and mortality world-wide. The COVID-19 pandemic caused by the novel SARS-like coronavirus (SARS-CoV-2) underscores the need to innovate and accelerate the development of effective vaccination strategies against EIDs. Human leukocyte antigen (HLA) molecules play a central role in the immune system by determining the peptide repertoire displayed to the T-cell compartment. Genetic polymorphisms of the HLA system thus confer a strong variability in vaccine-induced immune responses and may complicate the selection of vaccine candidates, because the distribution and frequencies of HLA alleles are highly variable among different ethnic groups. Herein, we build on the emerging paradigm of rational epitope-based vaccine design, by describing an immunoinformatics tool (Predivac-3.0) for proteome-wide T-cell epitope discovery that accounts for ethnic-level variations in immune responsiveness. Predivac-3.0 implements both CD8+ and CD4+ T-cell epitope predictions based on HLA allele frequencies retrieved from the Allele Frequency Net Database. The tool was thoroughly assessed, proving comparable performances (AUC ~0.9) against four state-of-the-art pan-specific immunoinformatics methods capable of population-level analysis (NetMHCPan-4.0, Pickpocket, PSSMHCPan and SMM), as well as a strong accuracy on proteome-wide T-cell epitope predictions for HIV-specific immune responses in the Japanese population. The utility of the method was investigated for the COVID-19 pandemic, by performing in silico T-cell epitope mapping of the SARS-CoV-2 spike glycoprotein according to the ethnic context of the countries where the ChAdOx1 vaccine is currently initiating phase III clinical trials. Potentially immunodominant CD8+ and CD4+ T-cell epitopes and population coverages were predicted for each population (the Epitope Discovery mode), along with optimized sets of broadly recognized (promiscuous) T-cell epitopes maximizing coverage in the target populations (the Epitope Optimization mode). Population-specific epitope-rich regions (T-cell epitope clusters) were further predicted in protein antigens based on combined criteria of epitope density and population coverage. Overall, we conclude that Predivac-3.0 holds potential to contribute in the understanding of ethnic-level variations of vaccine-induced immune responsiveness and to guide the development of epitope-based next-generation vaccines against emerging pathogens, whose geographic distributions and populations in need of vaccinations are often well-defined for regional epidemics.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/metabolismo , Grupos Étnicos , Antígenos HLA/metabolismo , Proteómica/métodos , Glicoproteína de la Espiga del Coronavirus/metabolismo , /epidemiología , Enfermedades Transmisibles Emergentes , Epítopos de Linfocito T/genética , Antígenos HLA/genética , Humanos , Inmunogenicidad Vacunal , Aplicaciones de la Informática Médica , Pandemias/prevención & control , Polimorfismo Genético , Unión Proteica , Programas Informáticos , Glicoproteína de la Espiga del Coronavirus/genética
19.
PLoS One ; 16(2): e0246320, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33529237

RESUMEN

Emerging infectious diseases such as Ebola Virus Disease (EVD), Nipah Virus Encephalitis and Lassa fever pose significant epidemic threats. Responses to emerging infectious disease outbreaks frequently occur in resource-constrained regions and under high pressure to quickly contain the outbreak prior to potential spread. As seen in the 2020 EVD outbreaks in the Democratic Republic of Congo and the current COVID-19 pandemic, there is a continued need to evaluate and address the ethical challenges that arise in the high stakes environment of an emerging infectious disease outbreak response. The research presented here provides analysis of the ethical challenges with regard to allocation of limited resources, particularly experimental therapeutics, using the 2013-2016 EVD outbreak in West Africa as a case study. In-depth semi-structured interviews were conducted with senior healthcare personnel (n = 16) from international humanitarian aid organizations intimately engaged in the 2013-2016 EVD outbreak response in West Africa. Interviews were recorded in private setting, transcribed, and iteratively coded using grounded theory methodology. A majority of respondents indicated a clear propensity to adopt an ethical framework of guiding principles for international responses to emerging infectious disease outbreaks. Respondents agreed that prioritization of frontline workers' access to experimental therapeutics was warranted based on a principle of reciprocity. There was widespread acceptance of adaptive trial designs and greater trial transparency in providing access to experimental therapeutics. Many respondents also emphasized the importance of community engagement in limited resource allocation scheme design and culturally appropriate informed consent procedures. The study results inform a potential ethical framework of guiding principles based on the interview participants' insights to be adopted by international response organizations and their healthcare workers in the face of allocating limited resources such as experimental therapeutics in future emerging infectious disease outbreaks to ease the moral burden of individual healthcare providers.


Asunto(s)
Enfermedades Transmisibles Emergentes/terapia , Brotes de Enfermedades/ética , Asignación de Recursos para la Atención de Salud/ética , Fiebre Hemorrágica Ebola/terapia , Ensayos Clínicos Adaptativos como Asunto/ética , Adulto , África Occidental/epidemiología , Femenino , Personal de Salud/ética , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Terapias en Investigación/ética
20.
ACS Synth Biol ; 10(2): 379-390, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33534552

RESUMEN

Generating and characterizing immunoreagents to enable studies of novel emerging viruses is an area where ensembles of synthetic genes, recombinant antibody pipelines, and modular antibody-reporter fusion proteins can respond rapidly. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread through the global population causing widespread morbidity, mortality, and socioeconomic chaos. Using SARS-CoV-2 as our model and starting with a gBlocks encoded nucleocapsid (N) gene, we purified recombinant protein from E. coli, to serve as bait for selecting semisynthetic nanobodies from our Nomad single-pot library. Clones were isolated in days and first fused to Gaussia luciferase to determine EC50 in the tens of nM range, and second fused to the ascorbate peroxidase derivative APEX2 for sensitive detection of SARS-CoV-2 infected cells. To generate inherently fluorescent immunoreagents, we introduce novel periplasmic sdAb fusions made with mNeonGreen and mScarlet-I, which were produced at milligram amounts. The fluorescent fusion proteins enabled concise visualization of SARS-CoV-2 N in the cytoplasm but not in the nucleus 24 h post infection, akin to the distribution of SARS-CoV N, thereby validating these useful imaging tools. SdAb reactivity appeared specific to SARS-CoV-2 with very much weaker binding to SARS-CoV, and no noticeable cross-reactivity to a panel of overexpressed human codon optimized N proteins from other CoV. High periplasmic expression levels and in silico immortalization of the nanobody constructs guarantees a cost-effective and reliable source of SARS-CoV-2 immunoreagents. Our proof-of-principle study should be applicable to known and newly emerging CoV to broaden the tools available for their analysis and help safeguard human health in a more proactive than reactive manner.


Asunto(s)
/epidemiología , /genética , Sondas Moleculares/genética , Pandemias , /inmunología , Anticuerpos Antivirales/genética , Especificidad de Anticuerpos/genética , Enfermedades Transmisibles Emergentes/virología , Escherichia coli/genética , Técnica del Anticuerpo Fluorescente , Genes Sintéticos , Genes Virales , Células HEK293 , Humanos , Sondas Moleculares/inmunología , Pandemias/prevención & control , Biblioteca de Péptidos , Fosfoproteínas/genética , Fosfoproteínas/inmunología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Anticuerpos de Dominio Único/genética , Biología Sintética
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