The Experts below are selected from a list of 2928 Experts worldwide ranked by ideXlab platform
Marie-paule Kieny - One of the best experts on this subject based on the ideXlab platform.
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Lessons learned from Ebola Vaccine R&D during a public health emergency
Human Vaccines & Immunotherapeutics, 2018Co-Authors: Marie-paule KienyAbstract:In spite of a complete lack of Research and Development (R&D) preparedness, the 2013-2016 West-Africa Ebola experience demonstrated that it is possible to compress R&D timelines to less than a single year, from a more usual decade or longer. This is mostly to be credited to an unprecedented collaborative effort building on the availability of a small number of candidate diagnostic tests, drugs and Vaccines that could be moved rapidly into the clinical phase evaluation. The World Health Organization (WHO) led international consultations and activities - including the organization of a successful Ebola Vaccine efficacy trial in Guinea - as a contribution to the unprecedented global efforts to control the Ebola epidemic. Since 2015, WHO expert teams and partners are implementing a novel R&D model for emerging infectious pathogens which are the most likely to cause severe outbreaks in the future, and for which no or only few medical countermeasures are available: the WHO R&D Blueprint. The objective for the Blueprint is the fostering of a R&D environment which is prepared for quickly and effectively responding to outbreaks due to emerging infectious disease.
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on a path to accelerate access to Ebola Vaccines the who s research and development efforts during the 2014 2016 Ebola epidemic in west africa
Current Opinion in Virology, 2016Co-Authors: Ana Maria Henaorestrepo, Vasee S Moorthy, Mariepierre Preziosi, David Wood, Marie-paule KienyAbstract:During 2014 and 2015 an outbreak of Ebola deemed a Public Health Emergency of International Concern affected a number of West African countries. The outbreak underscored the need for a Vaccine against Ebola. An unprecedented and to great extent collaborative effort built on the availability of a number of candidate Vaccines that could enter into clinical phase evaluation. A series of international consultations and activities were led by WHO as a contribution to the unprecedented global efforts to develop and assess an Ebola Vaccine. WHO consulted widely, and immediately fostered interactions with the international scientific, ethics, regulatory, Vaccine development, public health partners, industry and funders’ communities and participated in consortia to facilitate Ebola Vaccine assessments. WHO also fostered key activities to ensure the optimal policy and deployment of Ebola Vaccines, if licensed. WHO has convened a broad global coalition of experts to develop a Blueprint and a platform for accelerated R&D, in order to avert full-blown epidemics.
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Ebola Vaccine — An Urgent International Priority
New England Journal of Medicine, 2014Co-Authors: Rupa Kanapathipillai, David Wood, Ana Maria Henao Restrepo, Christopher Dye, Marie-paule KienyAbstract:With the Ebola epidemic in West Africa continuing to grow, the World Health Organization convened an urgent meeting on September 29 and 30 to assess the efforts under way to evaluate and produce safe and effective Ebola Vaccines as soon as possible.
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Ebola Vaccine an urgent international priority
The New England Journal of Medicine, 2014Co-Authors: Rupa Kanapathipillai, David Wood, Ana Maria Henao Restrepo, Christopher Dye, Marie-paule KienyAbstract:With the Ebola epidemic in West Africa continuing to grow, the World Health Organization convened an urgent meeting on September 29 and 30 to assess the efforts under way to evaluate and produce safe and effective Ebola Vaccines as soon as possible.
Johnarne Rottingen - One of the best experts on this subject based on the ideXlab platform.
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stability of a vesicular stomatitis virus vectored Ebola Vaccine
The Journal of Infectious Diseases, 2016Co-Authors: Marianne Arnemo, Sara Viksmoen Watle, Kristin Merete Schoultz, Kirsti Vainio, Gunnstein Norheim, Vasee S Moorthy, Patricia E Fast, Johnarne RottingenAbstract:: The live attenuated vesicular stomatitis virus-vectored Ebola Vaccine rVSV-ZEBOV is currently undergoing clinical trials in West Africa. The Vaccine is to be stored at -70°C or less. Since maintaining the cold chain is challenging in rural areas, the rVSV-ZEBOV Vaccine's short-term and long-term stability at different temperatures was examined. Different dilutions were tested since the optimal Vaccine dosage had not yet been determined at the start of this experiment. The results demonstrate that the original Vaccine formulation was stable for 1 week at 4°C and for 24 hours at 25°C. The stability of the Vaccine was compromised by both high temperatures and dilution.
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Stability of a Vesicular Stomatitis Virus–Vectored Ebola Vaccine
Journal of Infectious Diseases, 2015Co-Authors: Marianne Arnemo, Sara Viksmoen Watle, Kristin Merete Schoultz, Kirsti Vainio, Gunnstein Norheim, Vasee S Moorthy, Patricia E Fast, Johnarne Rottingen, Tor GjøenAbstract:The live attenuated vesicular stomatitis virus-vectored Ebola Vaccine rVSV-ZEBOV is currently undergoing clinical trials in West Africa. The Vaccine is to be stored at -70°C or less. Since maintaining the cold chain is challenging in rural areas, the rVSV-ZEBOV Vaccine's short-term and long-term stability at different temperatures was examined. Different dilutions were tested since the optimal Vaccine dosage had not yet been determined at the start of this experiment. The results demonstrate that the original Vaccine formulation was stable for 1 week at 4°C and for 24 hours at 25°C. The stability of the Vaccine was compromised by both high temperatures and dilution.
Claire-anne Siegrist - One of the best experts on this subject based on the ideXlab platform.
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Volunteer feedback and perceptions after participation in a phase I, first-in-human Ebola Vaccine trial: An anonymous survey.
PLOS ONE, 2017Co-Authors: Julie-anne Dayer, Claire-anne Siegrist, Angela HuttnerAbstract:The continued participation of volunteers in clinical trials is crucial to advances in healthcare. Few data are available regarding the satisfaction and impressions of healthy volunteers after participation in phase I trials, many of which lead to unexpected adverse events. We report feedback from over 100 adult volunteers who took part in a first-in-human trial conducted in a high-income country testing an experimental Ebola Vaccine causing significant reactogenicity, as well as unexpected arthritis in one fifth of participants. The anonymous, internet-based satisfaction survey was sent by email to all participants upon their completion of this one-year trial; it asked 24 questions concerning volunteers' motivations, impressions of the trial experience, and overall satisfaction. Answers were summarized using descriptive statistics. Of the 115 trial participants, 103 (90%) filled out the survey. Fifty-five respondents (53%) were male. Thirty-five respondents (34%) were healthcare workers, many of whom would deploy to Ebola-affected countries. All respondents cited scientific advancement as their chief motivation for participation, while 100/103 (97%) and 61/103 (59%) reported additional "humanitarian reasons" and potential protection from Ebolavirus, respectively. Although investigators had documented adverse events in 97% of trial participants, only 74 of 103 respondents (72%) recalled experiencing an adverse event. All reported an overall positive experience, and 93/103 (90%) a willingness to participate in future trials. Given the high level of satisfaction, no significant associations could be detected between trial experiences and satisfaction, even among respondents reporting adverse events lasting weeks or months. Despite considerable reactogenicity and unexpected Vaccine-related arthritis, all survey respondents reported overall satisfaction. While this trial's context was unique, the positive feedback is likely due at least in part to the intense communication of trial information to participants, which included both general findings and personalized results.
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Immunomonitoring of human responses to the rVSV-ZEBOV Ebola Vaccine.
Current Opinion in Virology, 2017Co-Authors: Donata Medaglini, Claire-anne SiegristAbstract:The rVSV-ZEBOV Vaccine is currently the only Ebola Vaccine with demonstrated clinical efficacy in a ring-vaccination clinical trial. It has been shown to be reactogenic but immunogenic and safe in several Phase I clinical studies. However, its mechanisms of protection are unknown and available immunogenicity data are mostly limited to classical serological analysis; it is now of paramount importance to apply cutting-edge technologies, including transcriptomic and metabolomic analyses, and to perform integrative analyses with standard serology and clinical data to comprehensively profile the rVSV-ZEBOV immune signature.
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Ebola Vaccine r d filling the knowledge gaps
Science Translational Medicine, 2015Co-Authors: Donata Medaglini, Ali M Harandi, Tom H M Ottenhoff, Claire-anne SiegristAbstract:With an emphasis on systems analyses, the VSV-EBOVAC project harnesses state-of-the-art technologies that illuminate mechanisms behind the observed immunogenicity and reactogenicity of the rVSV-ZEBOV Vaccine and ensures that such information is shared among stakeholders.
David Wood - One of the best experts on this subject based on the ideXlab platform.
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on a path to accelerate access to Ebola Vaccines the who s research and development efforts during the 2014 2016 Ebola epidemic in west africa
Current Opinion in Virology, 2016Co-Authors: Ana Maria Henaorestrepo, Vasee S Moorthy, Mariepierre Preziosi, David Wood, Marie-paule KienyAbstract:During 2014 and 2015 an outbreak of Ebola deemed a Public Health Emergency of International Concern affected a number of West African countries. The outbreak underscored the need for a Vaccine against Ebola. An unprecedented and to great extent collaborative effort built on the availability of a number of candidate Vaccines that could enter into clinical phase evaluation. A series of international consultations and activities were led by WHO as a contribution to the unprecedented global efforts to develop and assess an Ebola Vaccine. WHO consulted widely, and immediately fostered interactions with the international scientific, ethics, regulatory, Vaccine development, public health partners, industry and funders’ communities and participated in consortia to facilitate Ebola Vaccine assessments. WHO also fostered key activities to ensure the optimal policy and deployment of Ebola Vaccines, if licensed. WHO has convened a broad global coalition of experts to develop a Blueprint and a platform for accelerated R&D, in order to avert full-blown epidemics.
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Ebola Vaccine — An Urgent International Priority
New England Journal of Medicine, 2014Co-Authors: Rupa Kanapathipillai, David Wood, Ana Maria Henao Restrepo, Christopher Dye, Marie-paule KienyAbstract:With the Ebola epidemic in West Africa continuing to grow, the World Health Organization convened an urgent meeting on September 29 and 30 to assess the efforts under way to evaluate and produce safe and effective Ebola Vaccines as soon as possible.
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Ebola Vaccine an urgent international priority
The New England Journal of Medicine, 2014Co-Authors: Rupa Kanapathipillai, David Wood, Ana Maria Henao Restrepo, Christopher Dye, Marie-paule KienyAbstract:With the Ebola epidemic in West Africa continuing to grow, the World Health Organization convened an urgent meeting on September 29 and 30 to assess the efforts under way to evaluate and produce safe and effective Ebola Vaccines as soon as possible.
Rodolphe Thiébaut - One of the best experts on this subject based on the ideXlab platform.
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Dynamics of the Humoral Immune Response to a Prime-Boost Ebola Vaccine: Quantification and Sources of Variation
Journal of Virology, 2019Co-Authors: Chloé Pasin, Macaya Douoguih, Irene Balelli, Thierry Van Effelterre, Viki Bockstal, Laura Solforosi, Mélanie Prague, Rodolphe ThiébautAbstract:The Ebola Vaccine based on Ad26.ZEBOV/MVA-BN-Filo prime-boost regimens is being evaluated in multiple clinical trials. The long-term immune response to the Vaccine is unknown, including factors associated with the response and variability around the response. We analyzed data from three phase 1 trials performed by the EBOVAC1 Consortium in four countries: the United Kingdom, Kenya, Tanzania, and Uganda. Participants were randomized into four groups based on the interval between prime and boost immunizations (28 or 56 days) and the sequence in which Ad26.ZEBOV and MVA-BN-Filo were administered. Consecutive enzyme-linked immunosorbent assay (ELISA) measurements of the IgG binding antibody concentrations against the Kikwit glycoprotein (GP) were available for 177 participants to assess the humoral immune response up to 1 year postprime. Using a mathematical model for the dynamics of the humoral response, from 7 days after the boost immunization up to 1 year after the prime immunization, we estimated the durability of the antibody response and the influence of different factors on the dynamics of the humoral response. Ordinary differential equations (ODEs) described the dynamics of antibody response and two populations of antibody-secreting cells (ASCs), short-lived (SL) and long-lived (LL). Parameters of the ODEs were estimated using a population approach. We estimated that half of the LL ASCs could persist for at least 5 years. The Vaccine regimen significantly affected the SL ASCs and the antibody peak but not the long-term response. The LL ASC compartment dynamics differed significantly by geographic regions analyzed, with a higher long-term antibody persistence in European subjects. These differences could not be explained by the observed differences in cellular immune response.
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Dynamics of the Humoral Immune Response to a Prime-Boost Ebola Vaccine: Quantification and Sources of Variation.
Journal of Virology, 2019Co-Authors: Chloé Pasin, Macaya Douoguih, Irene Balelli, Thierry Van Effelterre, Viki Bockstal, Laura Solforosi, Mélanie Prague, Rodolphe ThiébautAbstract:The Ebola Vaccine based on Ad26.ZEBOV/MVA-BN-Filo prime-boost regimens is being evaluated in multiple clinical trials. The long-term immune response to the Vaccine is unknown, including factors associated with the response and variability around the response. We analyzed data from three phase 1 trials performed by the EBOVAC1 Consortium in four countries: the United Kingdom, Kenya, Tanzania, and Uganda. Participants were randomized into four groups based on the interval between prime and boost immunizations (28 or 56 days) and the sequence in which Ad26.ZEBOV and MVA-BN-Filo were administered. Consecutive enzyme-linked immunosorbent assay (ELISA) measurements of the IgG binding antibody concentrations against the Kikwit glycoprotein (GP) were available for 177 participants to assess the humoral immune response up to 1 year postprime. Using a mathematical model for the dynamics of the humoral response, from 7 days after the boost immunization up to 1 year after the prime immunization, we estimated the durability of the antibody response and the influence of different factors on the dynamics of the humoral response. Ordinary differential equations (ODEs) described the dynamics of antibody response and two populations of antibody-secreting cells (ASCs), short-lived (SL) and long-lived (LL). Parameters of the ODEs were estimated using a population approach. We estimated that half of the LL ASCs could persist for at least 5 years. The Vaccine regimen significantly affected the SL ASCs and the antibody peak but not the long-term response. The LL ASC compartment dynamics differed significantly by geographic regions analyzed, with a higher long-term antibody persistence in European subjects. These differences could not be explained by the observed differences in cellular immune response. IMPORTANCE With no available licensed Vaccines or therapies, the West African Ebola virus disease epidemic of 2014 to 2016 caused 11,310 deaths. Following this outbreak, the development of Vaccines has been accelerated. Combining different vector-based Vaccines as heterologous regimens could induce a durable immune response, assessed through antibody concentrations. Based on data from phase 1 trials in East Africa and Europe, the dynamics of the humoral immune response from 7 days after the boost immunization onwards were modeled to estimate the durability of the response and understand its variability. Antibody production is maintained by a population of long-lived cells. Estimation suggests that half of these cells can persist for at least 5 years in humans. Differences in prime-boost Vaccine regimens affect only the short-term immune response. Geographical differences in long-lived cell dynamics were inferred, with higher long-term antibody concentrations induced in European participants.
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Ebola Vaccine development: Systematic review of pre-clinical and clinical studies, and meta-analysis of determinants of antibody response variability after vaccination
International Journal of Infectious Diseases, 2018Co-Authors: Lise Gross, Édouard Lhomme, Chloé Pasin, Laura Richert, Rodolphe ThiébautAbstract:For Ebola Vaccine development, antibody response is a major endpoint although its determinants are not well known. We aimed to review Ebola Vaccine studies and to assess factors associated with antibody response variability in humans.
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Ebola Vaccine development: Systematic review of pre-clinical and clinical studies, and meta-analysis of determinants of antibody response variability after vaccination
International Journal of Infectious Diseases, 2018Co-Authors: Lise Gross, Édouard Lhomme, Chloé Pasin, Laura Richert, Rodolphe ThiébautAbstract:For Ebola Vaccine development, antibody response is a major endpoint although its determinants are not well known. We aimed to review Ebola Vaccine studies and to assess factors associated with antibody response variability in humans.
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Multi-block high-dimensional lasso-penalized analysis with imputation of missing data applied to postgenomic data in an Ebola Vaccine trial
2018Co-Authors: Hadrien Lorenzo, Rodolphe Thiébaut, Jérôme SaraccoAbstract:Several sets of variables can be analyzed simultaneously by canonical correlation in a multi-way analysis. These sets of variables are often high-dimensional and repeated over time. For instance, full-transcriptome measured by RNA-Seq used to be performed in longitudinal studies as well as other measures such as peptides or cells. Hence, canonical correlation analysis has been extended with regularized approaches to deal with several high dimensional data. However, some measurements can be missing for technical reasons and therefore introduce undesired structures due to the huge dimension of the datasets. Our objective is to find an efficient method allowing to impute the missing values taking into account the three-way structure, participant-transcriptome-time, and also the missing path structure. We proposed an EM-like covariance-maximization lasso-penalized high-dimensional completion matrix algorithm to reach that goal. We compared our approach on simulated data-sets with the mean imputation per gene pertime step, the missMDA-imputeMFA algorithm which takes structure into account and the softImpute solution initially designed to solve the Netix competition a high-dimensional problem. We used two criterions: the L2-error between estimated and simulated values and the L2-error between estimated and simulated covariance matrices. The numerical results exhibited the superiority of the proposed method in most of the scenarii. We also illustrated our approach on a real data-set from a phase I Ebola Vaccine trial measuring RNA-Seq data after vaccination (richtien, cell report 2017) in 20 participants at 4 different times on whole-blood samples, representing 74 sequenced-samples, among which 24 samples were missing because of technological issues.