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1.
Nat Commun ; 15(1): 7666, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227399

RESUMEN

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck's Ervebo (rVSV-ZEBOV) and Johnson & Johnson's two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26-MVA, rVSV, and rVSV-booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination.


Asunto(s)
Linfocitos T CD4-Positivos , Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Inmunidad Celular , Humanos , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Vacunas contra el Virus del Ébola/inmunología , Vacunas contra el Virus del Ébola/administración & dosificación , Ebolavirus/inmunología , Linfocitos T CD4-Positivos/inmunología , Femenino , Masculino , Adulto , Anticuerpos Antivirales/inmunología , Vacunación , Citocinas/metabolismo , Citocinas/inmunología , Estudios de Seguimiento , Persona de Mediana Edad , Células T de Memoria/inmunología , Inmunización Secundaria , Adulto Joven , Memoria Inmunológica/inmunología
2.
Emerg Microbes Infect ; 13(1): 2392651, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39155772

RESUMEN

Ebola disease is a lethal viral hemorrhagic fever caused by ebolaviruses within the Filoviridae family with mortality rates of up to 90%. Monoclonal antibody (mAb) based therapies have shown great potential for the treatment of EVD. However, the potential emerging ebolavirus isolates and the negative effect of decoy protein on the therapeutic efficacy of antibodies highlight the necessity of developing novel antibodies to counter the threat of Ebola. Here, 11 fully human mAbs were isolated from transgenic mice immunized with GP protein and recombinant vesicular stomatitis virus-bearing GP (rVSV-EBOV GP). These mAbs were divided into five groups according to their germline genes and exhibited differential binding activities and neutralization capabilities. In particular, mAbs 8G6, 2A4, and 5H4 were cross-reactive and bound at least three ebolavirus glycoproteins. mAb 4C1 not only exhibited neutralizing activity but no cross-reaction with sGP. mAb 7D8 exhibited the strongest neutralizing capacity. Further analysis on the critical residues for the bindings of 4C1 and 8G6 to GPs was conducted using antibodies complementarity-determining regions (CDRs) alanine scanning. It has been shown that light chain CDR3 played a crucial role in binding and neutralization and that any mutation in CDRs could not improve the binding of 4C1 to sGP. Importantly, mAbs 7D8, 8G6, and 4C1 provided complete protections against EBOV infection in a hamster lethal challenge model when administered 12 h post-infection. These results support mAbs 7D8, 8G6, and 4C1 as potent antibody candidates for further investigations and pave the way for further developments of therapies and vaccines.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Modelos Animales de Enfermedad , Ebolavirus , Fiebre Hemorrágica Ebola , Animales , Ebolavirus/inmunología , Ebolavirus/genética , Anticuerpos Monoclonales/inmunología , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/virología , Anticuerpos Antivirales/inmunología , Cricetinae , Ratones , Anticuerpos Neutralizantes/inmunología , Humanos , Ratones Transgénicos , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/genética , Reacciones Cruzadas
3.
JMIR Mhealth Uhealth ; 12: e53211, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39186366

RESUMEN

BACKGROUND: Mobile health (mHealth) technologies are increasingly used in contact tracing and case finding, enhancing and replacing traditional methods for managing infectious diseases such as Ebola, tuberculosis, COVID-19, and HIV. However, the variations in their development approaches, implementation scopes, and effectiveness introduce uncertainty regarding their potential to improve public health outcomes. OBJECTIVE: We conducted this systematic review to explore how mHealth technologies are developed, implemented, and evaluated. We aimed to deepen our understanding of mHealth's role in contact tracing, enhancing both the implementation and overall health outcomes. METHODS: We searched and reviewed studies conducted in Africa focusing on tuberculosis, Ebola, HIV, and COVID-19 and published between 1990 and 2023 using the PubMed, Scopus, Web of Science, and Google Scholar databases. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to review, synthesize, and report the findings from articles that met our criteria. RESULTS: We identified 11,943 articles, but only 19 (0.16%) met our criteria, revealing a large gap in technologies specifically aimed at case finding and contact tracing of infectious diseases. These technologies addressed a broad spectrum of diseases, with a predominant focus on Ebola and tuberculosis. The type of technologies used ranged from mobile data collection platforms and smartphone apps to advanced geographic information systems (GISs) and bidirectional communication systems. Technologies deployed in programmatic settings, often developed using design thinking frameworks, were backed by significant funding and often deployed at a large scale but frequently lacked rigorous evaluations. In contrast, technologies used in research settings, although providing more detailed evaluation of both technical performance and health outcomes, were constrained by scale and insufficient funding. These challenges not only prevented these technologies from being tested on a wider scale but also hindered their ability to provide actionable and generalizable insights that could inform public health policies effectively. CONCLUSIONS: Overall, this review underscored a need for organized development approaches and comprehensive evaluations. A significant gap exists between the expansive deployment of mHealth technologies in programmatic settings, which are typically well funded and rigorously developed, and the more robust evaluations necessary to ascertain their effectiveness. Future research should consider integrating the robust evaluations often found in research settings with the scale and developmental rigor of programmatic implementations. By embedding advanced research methodologies within programmatic frameworks at the design thinking stage, mHealth technologies can potentially become technically viable and effectively meet specific contact tracing health outcomes to inform policy effectively.


Asunto(s)
COVID-19 , Telemedicina , Tuberculosis , Humanos , África/epidemiología , Enfermedades Transmisibles/epidemiología , Trazado de Contacto/métodos , COVID-19/epidemiología , COVID-19/prevención & control , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Tuberculosis/epidemiología
4.
Health Secur ; 22(S1): S86-S96, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39137059

RESUMEN

This case study describes a feasibility assessment of a novel isolation care tent used in health facilities in Uganda during the 2022 Sudan ebolavirus outbreak. The Isolation System for Treatment and Agile Response to High-Risk Infections Model 1B (ISTARI 1B) is a single-occupancy, portable, negative-pressure isolation tent designed for the safe delivery of standard care to patients with a communicable disease, including Ebola disease (Sudan). At the request of the Uganda Ministry of Health, the Makerere University Infectious Diseases Institute and University of Nebraska Medical Center partnered to evaluate 7 health facilities across 4 districts in Uganda for infrastructure, case management, and infection prevention and control (IPC) capacity relevant to isolation care and ISTARI 1B use. A 3-day workshop was held with IPC leaders to provide familiarization and hands-on experience with the ISTARI 1B, delineate appropriate use scenarios in Ugandan healthcare settings, contextualize ISTARI 1B use in case management and IPC workflows, develop a framework for site assessment and implementation readiness, and consider ongoing monitoring, assessment, and intervention tools. Workshop participants performed a comprehensive site assessment and mock deployment of the ISTARI 1B. In this case study, we describe lessons learned from health facility assessments and workshop outcomes and offer recommendations to support successful ISTARI 1B implementation. Use scenarios and implementation strategies were identified across facility levels, including tools for site assessment, training, risk communication, and ongoing quality and safety monitoring.


Asunto(s)
Brotes de Enfermedades , Estudios de Factibilidad , Fiebre Hemorrágica Ebola , Uganda/epidemiología , Humanos , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/epidemiología , Brotes de Enfermedades/prevención & control , Aislamiento de Pacientes/métodos , Ebolavirus , Sudán/epidemiología , Instituciones de Salud , Control de Infecciones/métodos , Control de Infecciones/organización & administración
5.
Am J Trop Med Hyg ; 111(3): 578-588, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-38955200

RESUMEN

This study explored the experiences of healthcare providers (HCPs) and frontline workers who were involved in an Ebola vaccine trial in the Democratic Republic of the Congo. The researchers interviewed a total of 99 participants (HCPs and frontline workers) living and working in the Boende health district during the period of the study, from February to March 2022. These individuals included a mix of trial participants and non-trial participants (staff of the trial, local health authorities, and head nurses of health centers). In-depth individual interviews, as well as focus group discussions (FGDs), were used to understand interviewees' experiences and perceptions. The data were analyzed to identify the main themes. The findings unveiled a multitude of positive experiences among interviewees/FGD participants. The commitment of the trial investigators to improve the study site and to equip the volunteers with necessary skills and knowledge greatly contributed to a positive trial experience. However, some interviewees felt that the reimbursement for time and travel expenses during their trial visits was insufficient in comparison with their expectations. Additionally, there were expressions of worry about the frequency of blood draws during scheduled trial visits. Our findings emphasize the critical importance of addressing and continuously considering the perspectives and concerns of trial participants before designing and implementing vaccine trials. By actively incorporating their inputs, researchers can mitigate concerns and tailor communication strategies, potentially enhancing the overall success and impact of the vaccine trial.


Asunto(s)
Vacunas contra el Virus del Ébola , Personal de Salud , Fiebre Hemorrágica Ebola , Humanos , República Democrática del Congo , Vacunas contra el Virus del Ébola/administración & dosificación , Personal de Salud/psicología , Fiebre Hemorrágica Ebola/prevención & control , Femenino , Masculino , Adulto , Actitud del Personal de Salud , Grupos Focales , Persona de Mediana Edad
6.
J Virol ; 98(8): e0124223, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39012096

RESUMEN

Sudan ebolavirus (SUDV) is a member of the genus Ebolavirus (Family Filoviridae) and has caused sporadic outbreaks of Ebola disease (EBOD), or more specifically Sudan virus disease (SVD), with high mortality rates in Africa. Current vaccines and therapies that have been developed for filoviruses are almost all specific for Ebola virus (EBOV; of the species Zaire ebolavirus), and there is a current lack of therapeutics specific for SUDV. The recent SUDV outbreak in Uganda, which was distributed across multiple districts, including Kampala, a densely populated urban center, highlights the critical need for the development of novel SUDV-specific or pan-Ebola virus therapeutics. Previous work has characterized two monoclonal antibodies, FVM04 and CA45, which have neutralization capabilities against both EBOV and SUDV and have shown protective efficacy in animal challenge studies. Here, we expand upon this work, showing that treatment with a monoclonal antibody cocktail consisting of FVM04 and CA45 provides full protection against lethal SUDV infection in cynomolgus macaques. Studies that evaluate outcomes at late time points after infection, once clinical signs of illness are apparent, are vital for assessing the therapeutic efficacy of antibody therapeutics. We have shown that when treatment is initiated as late as 5 days after infection, with a second dose given on day 8, that treated groups showed few clinical signs or morbidity, with complete survival. This work provides further evidence that FVM04 and CA45 have strong therapeutic potential against SUDV and their development as a pan-Ebola virus therapeutic should be pursued. IMPORTANCE: There are currently no approved vaccines or therapeutics for Sudan virus, a filovirus which is highly related to Ebola virus and causes similar disease and outbreaks. In this study, a cocktail of two potent monoclonal antibodies that effectively neutralize Sudan virus was tested in a nonhuman primate model of Sudan virus disease. Treatment was highly effective, even when initiated as late as 5 days after infection, when clinical signs of infection were already evident. All treated animals showed complete recovery from infection, with little evidence of disease, while all animals that received a control treatment succumbed to infection within 8 days. The study further demonstrated the strong therapeutic potential of the antibody treatment and supported further development for use in Sudan virus outbreaks.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , Ebolavirus , Fiebre Hemorrágica Ebola , Retraso del Tratamiento , Animales , Femenino , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Modelos Animales de Enfermedad , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Macaca fascicularis , Masculino
7.
Commun Biol ; 7(1): 871, 2024 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020082

RESUMEN

Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. At the same time, the role of the complement system remains unclear. Here, we compare complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of GP. Binding of GC-specific mAbs to GP induces complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs. In the mouse model of EBOV infection, depletion of the complement system leads to an impairment of protection exerted by one of the GC-specific, but not MPER-specific mAbs. Our data suggest that activation of the complement system represents an important mechanism of antiviral protection by GC antibodies.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , Ebolavirus , Fiebre Hemorrágica Ebola , Polisacáridos , Proteínas del Envoltorio Viral , Animales , Ebolavirus/inmunología , Anticuerpos Monoclonales/inmunología , Ratones , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/virología , Fiebre Hemorrágica Ebola/prevención & control , Polisacáridos/inmunología , Anticuerpos Antivirales/inmunología , Humanos , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/metabolismo , Activación de Complemento , Ratones Endogámicos BALB C , Femenino , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Glicoproteínas/inmunología
8.
Health Secur ; 22(S1): S45-S49, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39037030

RESUMEN

Developing and sustaining relationships and networks before an emergency occurs is crucial. The Biocontainment Unit Leadership Workgroup is a consortium of the 13 Regional Emerging Special Pathogen Treatment Centers in the United States. Established in 2017, the volunteer-based workgroup is composed of operational leaders dedicated to maintaining readiness for special pathogen care. Monthly meetings focus on addressing operational challenges, sharing best practices, and brainstorming solutions to common problems. Task forces are leveraged to tackle more complex issues that are identified as priorities. In 2022, members of the workgroup were harnessed for response efforts related to mpox, Sudan ebolavirus, and Marburg virus disease. The weekly Outbreak Readiness call is a shared effort between the Biocontainment Unit Leadership Workgroup and the Special Pathogens Research Network of the National Emerging Special Pathogens Training and Education Center. Call participants included leaders of the Regional Emerging Special Pathogen Treatment Centers and federal partners who shared weekly updates on operational readiness of units, case counts, laboratory capacity, available medical countermeasures, and other pertinent information. The routine exchange of real-time information enabled learning and collegial sharing of experiences, highlighted the experience of the network to federal partners, and provided situational awareness of special pathogen outbreaks across the country. The consortium enabled this rapid convening of partners to meet an urgent need for special pathogen response. The weekly Outbreak Readiness call is a communication model and scalable framework that serves both domestic preparedness efforts and international efforts should the need for a collaborative global response arise. In this case study, we describe the framework and experience of this partnership, along with the structure of rapid deployment for group convening.


Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Liderazgo , Humanos , Brotes de Enfermedades/prevención & control , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/epidemiología , Estados Unidos , Contención de Riesgos Biológicos/métodos , Enfermedad del Virus de Marburg/prevención & control
9.
J Math Biol ; 89(2): 25, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963509

RESUMEN

The Ebola virus disease (EVD) has been endemic since 1976, and the case fatality rate is extremely high. EVD is spread by infected animals, symptomatic individuals, dead bodies, and contaminated environment. In this paper, we formulate an EVD model with four transmission modes and a time delay describing the incubation period. Through dynamical analysis, we verify the importance of blocking the infection source of infected animals. We get the basic reproduction number without considering the infection source of infected animals. And, it is proven that the model has a globally attractive disease-free equilibrium when the basic reproduction number is less than unity; the disease eventually becomes endemic when the basic reproduction number is greater than unity. Taking the EVD epidemic in Sierra Leone in 2014-2016 as an example, we complete the data fitting by combining the effect of the media to obtain the unknown parameters, the basic reproduction number and its time-varying reproduction number. It is shown by parameter sensitivity analysis that the contact rate and the removal rate of infected group have the greatest influence on the prevalence of the disease. And, the disease-controlling thresholds of these two parameters are obtained. In addition, according to the existing vaccination strategy, only the inoculation ratio in high-risk areas is greater than 0.4, the effective reproduction number can be less than unity. And, the earlier the vaccination time, the greater the inoculation ratio, and the faster the disease can be controlled.


Asunto(s)
Número Básico de Reproducción , Ebolavirus , Fiebre Hemorrágica Ebola , Conceptos Matemáticos , Modelos Biológicos , Fiebre Hemorrágica Ebola/transmisión , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/epidemiología , Número Básico de Reproducción/estadística & datos numéricos , Humanos , Animales , Sierra Leona/epidemiología , Ebolavirus/patogenicidad , Ebolavirus/fisiología , Epidemias/estadística & datos numéricos , Epidemias/prevención & control , Simulación por Computador , Modelos Epidemiológicos , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricos
10.
Sci Adv ; 10(27): eado7576, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38959306

RESUMEN

Following the apparent final case in an Ebola virus disease (EVD) outbreak, the decision to declare the outbreak over must balance societal benefits of relaxing interventions against the risk of resurgence. Estimates of the end-of-outbreak probability (the probability that no future cases will occur) provide quantitative evidence that can inform the timing of an end-of-outbreak declaration. An existing modeling approach for estimating the end-of-outbreak probability requires comprehensive contact tracing data describing who infected whom to be available, but such data are often unavailable or incomplete during outbreaks. Here, we develop a Markov chain Monte Carlo-based approach that extends the previous method and does not require contact tracing data. Considering data from two EVD outbreaks in the Democratic Republic of the Congo, we find that data describing who infected whom are not required to resolve uncertainty about when to declare an outbreak over.


Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , República Democrática del Congo/epidemiología , Humanos , Ebolavirus , Cadenas de Markov , Método de Montecarlo
11.
Nat Commun ; 15(1): 5667, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971835

RESUMEN

Important policy questions during infections disease outbreaks include: i) How effective are particular interventions?; ii) When can resource-intensive interventions be removed? We used mathematical modelling to address these questions during the 2017 Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC). Eight cases occurred before 15 May 2017, when the Ebola Response Team (ERT; co-ordinated by the World Health Organisation and DRC Ministry of Health) was deployed to reduce transmission. We used a branching process model to estimate that, pre-ERT arrival, the reproduction number was R = 1.49 (95% credible interval ( 0.67, 2.81 ) ). The risk of further cases occurring without the ERT was estimated to be 0.97 (97%). However, no cases materialised, suggesting that the ERT's measures were effective. We also estimated the risk of withdrawing the ERT in real-time. By the actual ERT withdrawal date (2 July 2017), the risk of future cases without the ERT was only 0.01, indicating that the ERT withdrawal decision was safe. We evaluated the sensitivity of our results to the estimated R value and considered different criteria for determining the ERT withdrawal date. This research provides an extensible modelling framework that can be used to guide decisions about when to relax interventions during future outbreaks.


Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Humanos , Brotes de Enfermedades/prevención & control , República Democrática del Congo/epidemiología , Modelos Teóricos , Ebolavirus
12.
Front Immunol ; 15: 1383753, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39040106

RESUMEN

Outbreaks of Ebolaviruses, such as Sudanvirus (SUDV) in Uganda in 2022, demonstrate that species other than the Zaire ebolavirus (EBOV), which is currently the sole virus represented in current licensed vaccines, remain a major threat to global health. There is a pressing need to develop effective pan-species vaccines and novel monoclonal antibody-based therapeutics for Ebolavirus disease. In response to recent outbreaks, the two dose, heterologous Ad26.ZEBOV/MVA-BN-Filo vaccine regimen was developed and was tested in a large phase II clinical trial (EBL2001) as part of the EBOVAC2 consortium. Here, we perform bulk sequencing of the variable heavy chain (VH) of B cell receptors (BCR) in forty participants from the EBL2001 trial in order to characterize the BCR repertoire in response to vaccination with Ad26.ZEBOV/MVA-BN-Filo. We develop a comprehensive database, EBOV-AbDab, of publicly available Ebolavirus-specific antibody sequences. We then use our database to predict the antigen-specific component of the vaccinee repertoires. Our results show striking convergence in VH germline gene usage across participants following the MVA-BN-Filo dose, and provide further evidence of the role of IGHV3-15 and IGHV3-13 antibodies in the B cell response to Ebolavirus glycoprotein. Furthermore, we found that previously described Ebola-specific mAb sequences present in EBOV-AbDab were sufficient to describe at least one of the ten most expanded BCR clonotypes in more than two thirds of our cohort of vaccinees following the boost, providing proof of principle for the utility of computational mining of immune repertoires.


Asunto(s)
Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Receptores de Antígenos de Linfocitos B , Vacunación , Humanos , Vacunas contra el Virus del Ébola/inmunología , Vacunas contra el Virus del Ébola/administración & dosificación , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Ebolavirus/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Receptores de Antígenos de Linfocitos B/genética , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Biología Computacional/métodos , Adulto , Masculino , Linfocitos B/inmunología , Femenino , Minería de Datos
13.
Front Immunol ; 15: 1429909, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081315

RESUMEN

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4+ helper T (Th) cells induced by Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.


Asunto(s)
Anticuerpos Antivirales , Vacuna BCG , Vacunas contra el Virus del Ébola , Ebolavirus , Fiebre Hemorrágica Ebola , Animales , Ratones , Vacuna BCG/inmunología , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Vacunas contra el Virus del Ébola/inmunología , Vacunas contra el Virus del Ébola/administración & dosificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Linfocitos T Colaboradores-Inductores/inmunología , Vacunación/métodos , Ratones Endogámicos C57BL , Femenino , Humanos , Modelos Animales de Enfermedad , Receptores de IgG/inmunología , Desarrollo de Vacunas , Cambio de Clase de Inmunoglobulina , Inmunización
15.
PLoS Negl Trop Dis ; 18(6): e0011955, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38848434

RESUMEN

Ebolavirus disease (EVD) outbreaks have intermittently occurred since the first documented case in the 1970s. Due to its transmission characteristics, large outbreaks have not been observed outside Africa. However, within the continent, significant outbreaks have been attributed to factors such as endemic diseases with similar symptoms and inadequate medical infrastructure, which complicate timely diagnosis. In this study, we employed a stochastic modeling approach to analyze the spread of EVD during the early stages of an outbreak, with an emphasis on inherent risks. We developed a model that considers healthcare workers and unreported cases, and assessed the effect of non-pharmaceutical interventions (NPIs) using actual data. Our results indicate that the implementation of NPIs led to a decrease in the transmission rate and infectious period by 30% and 40% respectively, following the declaration of the outbreak. We also investigated the risks associated with delayed outbreak recognition. Our simulations suggest that, when accounting for NPIs and recognition delays, prompt detection could have resulted in a similar outbreak scale, with approximately 50% of the baseline NPIs effect. Finally, we discussed the potential effects of a vaccination strategy as a follow-up measure after the outbreak declaration. Our findings suggest that a vaccination strategy can reduce both the burden of NPIs and the scale of the outbreak.


Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Vacunación , Humanos , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Brotes de Enfermedades/prevención & control , Vacunación/estadística & datos numéricos , Procesos Estocásticos , Modelos Estadísticos , Ebolavirus/inmunología
16.
PLoS Pathog ; 20(6): e1012262, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38924060

RESUMEN

Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model.


Asunto(s)
Ebolavirus , Fiebre Hemorrágica Ebola , Fiebre de Lassa , Virus Lassa , Enfermedad del Virus de Marburg , Marburgvirus , Animales , Ratones , Ebolavirus/inmunología , Virus Lassa/inmunología , Marburgvirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Fiebre de Lassa/inmunología , Fiebre de Lassa/prevención & control , Enfermedad del Virus de Marburg/inmunología , Enfermedad del Virus de Marburg/prevención & control , Vacunas Virales/inmunología , Humanos , Vacunación , Femenino , Anticuerpos Antivirales/inmunología , Inmunogenicidad Vacunal , Vacunas contra el Virus del Ébola/inmunología
17.
Vaccine ; 42(22): 126031, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-38880693

RESUMEN

BACKGROUND: The rVSVΔG-ZEBOV-GP Ebola vaccine (rVSV-ZEBOV) has been used in response to Ebola disease outbreaks caused by Ebola virus (EBOV). Understanding Ebola knowledge, attitudes, and practices (KAP) and the long-term immune response following rVSV-ZEBOV are critical to inform recommendations on future use. METHODS: We administered surveys and collected blood samples from healthcare workers (HCWs) from seven Ugandan healthcare facilities. Questionnaires collected information on demographic characteristics and KAP related to Ebola and vaccination. IgG ELISA, virus neutralization, and interferon gamma ELISpot measured immunological responses against EBOV glycoprotein (GP). RESULTS: Overall, 37 % (210/565) of HCWs reported receiving any Ebola vaccination. Knowledge that rVSV-ZEBOV only protects against EBOV was low among vaccinated (32 %; 62/192) and unvaccinated (7 %; 14/200) HCWs. Most vaccinated (91 %; 192/210) and unvaccinated (92 %; 326/355) HCWs wanted to receive a booster or initial dose of rVSV-ZEBOV, respectively. Median time from rVSV-ZEBOV vaccination to sample collection was 37.7 months (IQR: 30.5, 38.3). IgG antibodies against EBOV GP were detected in 95 % (61/64) of HCWs with vaccination cards and in 84 % (162/194) of HCWs who reported receiving a vaccination. Geometric mean titer among seropositive vaccinees was 0.066 IU/mL (95 % CI: 0.058-0.076). CONCLUSION: As Uganda has experienced outbreaks of Sudan virus and Bundibugyo virus, for which rVSV-ZEBOV does not protect against, our findings underscore the importance of continued education and risk communication to HCWs on Ebola and other viral hemorrhagic fevers. IgG antibodies against EBOV GP were detected in most vaccinated HCWs in Uganda 2─4 years after vaccination; however, the duration and correlates of protection warrant further investigation.


Asunto(s)
Anticuerpos Antivirales , Vacunas contra el Virus del Ébola , Ebolavirus , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Fiebre Hemorrágica Ebola , Vacunación , Humanos , Personal de Salud/estadística & datos numéricos , Uganda , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Masculino , Femenino , Vacunas contra el Virus del Ébola/inmunología , Vacunas contra el Virus del Ébola/administración & dosificación , Adulto , Ebolavirus/inmunología , Anticuerpos Antivirales/sangre , Vacunación/métodos , Persona de Mediana Edad , Encuestas y Cuestionarios , Inmunoglobulina G/sangre , Adulto Joven
18.
BMJ Glob Health ; 9(6)2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38857947

RESUMEN

INTRODUCTION: Clear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic Republic of the Congo and formulate policy recommendations. METHODS: To evaluate the AC policy, we performed a longitudinal cohort study, nested in an open-label, single-centre, randomised Ebola vaccine trial conducted among healthcare personnel. Participants' demographic information, residence distance to the study site and details on the financial and/or medical support provided for any (serious) adverse events ((S)AE) were combined and analysed. To assess the feasibility of the AC policy, an expenditure analysis of the costs related to AC support outcomes was performed. RESULTS: Enrolment in this evaluation study started on 29 November 2021. The study lasted 11 months and included 655 participants from the Ebola vaccine trial. In total, 393 participants used the AC policy, mostly for AE management (703 AE and 94 SAE) via medication provided by the study pharmacy (75.3%). Men had a 35.2% (95% CI 4.0% to 56.6%) lower likelihood of reporting AE compared with women. Likewise, this was 32.3% lower (95% CI 5.8% to 51.4%) for facility-based compared with community-based healthcare providers. The daily AE reporting was 78.8% lower during the passive vs the active trial stage, and 97.4% lower during unscheduled vs scheduled visits (p<0.001). Participants living further than 10 km from the trial site more frequently reported the travel distance as a reason for not using the policy (p<0.04). In practice, only 1.1% of the operational trial budget was used for AC policy support. CONCLUSION: The trial design, study population and local health system impacted the use of the AC policy. Nonetheless, the AC policy implementation in this remote and resource-constrained setting was feasible, had negligible budgetary implications and contributed to participants' healthcare options and well-being.


Asunto(s)
Vacunas contra el Virus del Ébola , Humanos , Masculino , Femenino , Vacunas contra el Virus del Ébola/economía , Adulto , República Democrática del Congo , Estudios Longitudinales , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/economía , Política de Salud , Persona de Mediana Edad , Personal de Salud
19.
J Travel Med ; 31(5)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38861425

RESUMEN

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.


Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Viaje , Humanos , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Uganda/epidemiología , Brotes de Enfermedades/prevención & control , Medición de Riesgo/métodos , Estados Unidos/epidemiología , Masculino , Femenino , Adulto , Centers for Disease Control and Prevention, U.S. , Salud Pública/métodos , Persona de Mediana Edad , Ebolavirus , Adolescente , Adulto Joven
20.
J Infect Dev Ctries ; 18(4): 556-564, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38728629

RESUMEN

INTRODUCTION: Unrecognized Ebola Virus Disease (EVD) can lead to multiple chains of transmissions if the first caretakers are not trained and prepared. This study aimed to assess healthcare workers (HCWs) preparedness in private hospitals located in Kampala, to detect, respond and prevent EVD. METHODOLOGY: A descriptive cross-sectional study was carried out among HCWs in direct clinical care provision in four private hospitals, and in one Ebola Treatment Unit (ETU) using a self-administered questionnaire from March to June 2020. RESULTS: 222 HCWs agreed to participate aged from 19 to 64 years and with 6 months to 38 years of practice where most were nurses (44%). 3/5 hospitals did not have written protocols on EVD case management, and only one (ETU) had an exclusive emergency team. 59% were not sure whether contact tracing was taking place. Private hospitals were not included in EVD trainings organized by the Ministry of Health (MoH). In addition, HCWs in private hospitals were not empowered by the MoH to take part in EVD case management. Despite these shortcomings, only 66% of HCWs showed an interest to be immunized. Knowledge about potential Ebola vaccines was generally poor. CONCLUSIONS: In Kampala, Uganda, establishment of a more comprehensive preparedness and response strategy for EVD outbreaks is imperative for HCWs in private facilities, including a wide vaccination educational program on Ebola vaccination. The findings from this study if addressed will likely improve the preparedness and management of future Ebola outbreaks in Uganda.


Asunto(s)
Personal de Salud , Fiebre Hemorrágica Ebola , Hospitales Privados , Humanos , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/epidemiología , Uganda/epidemiología , Estudios Transversales , Personal de Salud/estadística & datos numéricos , Adulto , Hospitales Privados/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Femenino , Adulto Joven , Encuestas y Cuestionarios , Epidemias/prevención & control
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