12 research outputs found

    Upper respiratory tract mucosal immunity for SARS-CoV-2 vaccines

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    SARS-CoV-2 vaccination significantly reduces morbidity and mortality, but has less impact on viral transmission rates, thus aiding viral evolution; and the longevity of vaccine-induced immunity rapidly declines. Immune responses in respiratory tract mucosal tissues are crucial for early control of infection, and can generate long-term antigen-specific protection with prompt recall responses. However, currently approved SARS-CoV-2 vaccines are not amenable to adequate respiratory mucosal delivery, particularly in the upper airways, which could account for the high vaccine breakthrough infection rates and limited duration of vaccine-mediated protection. In view of these drawbacks, we outline a strategy that has the potential to enhance both the efficacy and durability of existing SARS-CoV-2 vaccines, by inducing robust memory responses in the upper respiratory tract mucosa

    Severe COVID-19 versus multisystem inflammatory syndrome:comparing two critical outcomes of SARS-CoV-2 infection

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    peer reviewedSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with diverse host response immunodynamics and variable inflammatory manifestations. Several immune-modulating risk factors can contribute to a more severe coronavirus disease 2019 (COVID-19) course with increased morbidity and mortality. The comparatively rare post-infectious multisystem inflammatory syndrome (MIS) can develop in formerly healthy individuals, with accelerated progression to life-threatening illness. A common trajectory of immune dysregulation forms a continuum of the COVID-19 spectrum and MIS; however, severity of COVID-19 or the development of MIS is dependent on distinct aetiological factors that produce variable host inflammatory responses to infection with different spatiotemporal manifestations, a comprehensive understanding of which is necessary to set better targeted therapeutic and preventative strategies for both

    COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

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    Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective

    Deep phenotyping characterization of human unconventional CD8+NKG2A/C+ T cells among T and NK cells by spectral flow cytometry

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    Summary: Here, we present a protocol for setting three spectral flow cytometry panels for the characterization of human unconventional CD8+NKG2A/C+ T cells as well as other T and natural killer cell subsets. We describe steps for standardizing, preparing, and staining the cells, the experimental setup, and the final data analysis. This protocol should be advantageous in various settings including immunophenotyping of limited samples, immune function evaluation/monitoring, as well as research in oncology, autoimmune, and infectious diseases. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

    Interests of the Non-Human Primate Models for HIV Cure Research

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    International audienceNon-human primate (NHP) models are important for vaccine development and also contribute to HIV cure research. Although none of the animal models are perfect, NHPs enable the exploration of important questions about tissue viral reservoirs and the development of intervention strategies. In this review, we describe recent advances in the use of these models for HIV cure research and highlight the progress that has been made as well as limitations using these models. The main NHP models used are (i) the macaque, in which simian immunodeficiency virus (SIVmac) infection displays similar replication profiles as to HIV in humans, and (ii) the macaque infected by a recombinant virus (SHIV) consisting of SIVmac expressing the HIV envelope gene serving for studies analyzing the impact of anti-HIV Env broadly neutralizing antibodies. Lessons for HIV cure that can be learned from studying the natural host of SIV are also presented here. An overview of the most promising and less well explored HIV cure strategies tested in NHP models will be given

    Author Correction: COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms

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    International audienceFollowing publication, it was found that one of Alexander Mazein's affiliations was missing and the affiliation, Barcelona Supercomputing Center (BSC) was incorrectly spelled. It was also found that a part of the Acknowledgements section and a part of the Competing Interests section were missing. Both the HTML and PDF versions have been updated to reflect these changes

    COVID-19 Disease map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms

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    CITATION: Ostaszewski, M. et al. 2020. COVID-19 Disease map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms. Scientific Data, 7:136, doi:10.1038/s41597-020-0477-8.The original publication is available at https://www.nature.com/sdataWe announce the COVID-19 Disease Map (https://doi.org/10.17881/covid19-disease-map), an effort to build a comprehensive, standardized knowledge repository of SARS-CoV-2 virus-host interaction mechanisms, guided by input from domain experts and based on published work. This knowledge, available in the vast body of existing literature1,2 and the fast-growing number of new SARS-CoV-2 publications, needs rigorous and efficient organization in both human and machine-readable formats.Publisher's versio

    Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021

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    Despite the success of antiretroviral therapy (ART) for people living with HIV, lifelong treatment is required and there is no cure. HIV can integrate in the host genome and persist for the life span of the infected cell. These latently infected cells are not recognized as foreign because they are largely transcriptionally silent, but contain replication-competent virus that drives resurgence of the infection once ART is stopped. With a combination of immune activators, neutralizing antibodies, and therapeutic vaccines, some nonhuman primate models have been cured, providing optimism for these approaches now being evaluated in human clinical trials. In vivo delivery of gene-editing tools to either target the virus, boost immunity or protect cells from infection, also holds promise for future HIV cure strategies. In this Review, we discuss advances related to HIV cure in the last 5 years, highlight remaining knowledge gaps and identify priority areas for research for the next 5 years.Fil: Deeks, Steven G.. University of California; Estados UnidosFil: Archin, Nancie. University of North Carolina; Estados UnidosFil: Cannon, Paula. University of Southern California; Estados UnidosFil: Collins, Simon. Hiv I-base; Reino UnidoFil: Jones, R. Brad. Cornell University; Estados UnidosFil: de Jong, Marein A. W. P.. Aidsfonds; Países BajosFil: Lambotte, Olivier. Universite Paris-Saclay;Fil: Lamplough, Rosanne. International AIDS Society; SuizaFil: Ndung’u, Thumbi. University College London; Estados Unidos. Ragon Institute of MGH; Estados Unidos. University of KwaZulu-Natal; SudáfricaFil: Sugarman, Jeremy. University Johns Hopkins; Estados UnidosFil: Tiemessen, Caroline T.. University of the Witwatersrand; SudáfricaFil: Vandekerckhove, Linos. University of Ghent; BélgicaFil: Lewin, Sharon R.. The Peter Doherty Institute For Infection And Immunity; Australia. Monash University; Australia. University of Melbourne; AustraliaFil: Deeks, Steven. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: de Jong, Marein. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Ndhlovu, Zaza. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Chomont, Nicolas. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Brumme, Zabrina. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Deng, Kai. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Jasenosky, Luke. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Jefferys, Richard. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Orta Resendiz, Aurelio. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Mardarelli, Frank. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Nijhuis, Monique. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Bar, Katharine. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Howell, Bonnie. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Schneider, Alex. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Nabatanzi, Rose. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados UnidosFil: Blankson, Joel. The International AIDS Society (IAS) Global Scientific Strategy working group; Estados Unido
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