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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 (URT) mucosa.

Severe 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.

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. An effective and scalable cure strategy is a top priority for the HIV research field; this Review discusses recent advances, knowledge gaps, and priority research areas for the next 5 years.

International audience; Non-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.

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. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in the enrichment and validation of the curated mechanisms. We describe the contents of the Map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases and highlight new testable hypotheses.; 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. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in the enrichment and validation of the curated mechanisms. We describe the contents of the Map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases and highlight new testable hypotheses.

The human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the COVID-19 (coronavirus disease 2019) pandemic, has a vast heterogeneity of host responses, with resulting symptoms ranging from an asymptomatic phenotype, to a mild−moderate disease course, to a severe or critical disease status with significant hypoxia accompanied by acute respiratory distress syndrome, extensive pulmonary damage, and circulatory and multiorgan failure. SARS-CoV-2 infection is associated with several susceptibility factors that can contribute to a more severe clinical disease course with increased morbidity and mortality.These include age-related susceptibility (most prominent in the elderly and in infants), underlying chronic diseases and/or a compromised immune system, male sex, pregnancy and the postpartum period, specific ABO blood groups, several respiratory conditions, as well as high occupational viral exposure. However, a severe and novel disorder, termed multisystem inflammatory syndrome in children (MIS-C) and adults (MIS-A), can develop following SARS-CoV-2 infection in previously healthy individuals, which can rapidly progress to critical illness with hyperinflammatory processes leading to multiorgan damage. Furthermore, genetic factors may also influence susceptibility to SARS-CoV-2 infection and COVID-19 severity, the identification of which could prove useful as biomarkers to identify individuals at greater risk of severe disease or MIS-C/MIS-A development. Here, we aim to define (a) the immunodynamics of the range of host immune responses to SARS-CoV-2 infection, (b) how the various susceptibility factors mechanistically influence these immunodynamics, with converging mechanisms between the susceptible demographic groups contributing to a severe disease phenotype or MIS-C/MIS-A, and (c) and how these immunodynamics could inform the development of long-term immunotherapeutic strategies., Additional PDF notes available, as not all details included within the video presentation.

International audience; Following 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.

Researchers around the world join forces to reconstruct the molecular processes of the virus-host interactions aiming to combat the cause of the ongoing pandemic.

Background The main cause of the persistently high levels of immune activation in HIV positive patients undergoing suppressive chronic cART is still unknown. Previous findings have suggested a link between ongoing residual viral replication originating from the HIV reservoir and the immune activation levels. However, there is no clear evidence of this assumption. The aim of this study was to investigate the correlation between the reservoir and the levels of immune activation in chronic patients under fully suppressive cART. Methods We conducted a prospective longitudinal study in a cohort of HIV positive patients undergoing cART for more than 5 years without any documented blips. We quantified the HIV proviral DNA and the 2-LTR circles loads from PBMCs, the levels of immune activation and proliferation markers of T-cells (CD38+, Ki-67+), and the levels of plasmatic IL-7 at enrollment and 1-year of follow-up. Correlation analysis and group comparison were performed. Results 29 participants with a median of 8 years (IQR, 6.9-9.4) under suppressive cART were enrolled and successfully followed at 1 year. In this cohort, we found higher levels of CD8+ T-cell activation (CD38+) after 1-year (P = .000). There was a very weak correlation between the levels of immune activation and the proviral DNA of CD4+ T-cell and CD8+ T-cell. The levels of Ki-67+ T-cells declined on time without significant differences, and there was no significant correlation with the proportion of activated T-cells. The plasmatic levels of IL-7 decreased at the follow-up observation (P = .094), but there was no correlation with the levels of immune activation either. Conclusions We found a weak correlation of the levels of CD4+ and CD8+ T-cell activation with the proviral DNA and 2-LTR circles. This suggests the likely occurrence of further mechanisms driving chronic versus early immune activation other than viral replication by itself in subjects under chronic suppressive cART. More importantly, we highlight the relevance of decreasing T-cell activation in chronic patients to lower the risk of morbidity and early mortality by investigating other activation pathways in specifically chronic phases.