Mucosal bivalent live attenuated vaccine protects against human metapneumovirus and respiratory syncytial virus in mice.

Live-Attenuated Vaccines (LAVs) stimulate robust mucosal and cellular responses and have the potential to protect against Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV), the main etiologic agents of viral bronchiolitis and pneumonia in children. We inserted the RSV-F gene into an HMPV-based LAV (Metavac®) we previously validated for the protection of mice against HMPV challenge, and rescued a replicative recombinant virus (Metavac®-RSV), exposing both RSV- and HMPV-F proteins at the virion surface and expressing them in reconstructed human airway epithelium models. When administered to BALB/c mice by the intranasal route, bivalent Metavac®-RSV demonstrated its capacity to replicate with reduced lung inflammatory score and to protect against both RSV and lethal HMPV challenges in vaccinated mice while inducing strong IgG and broad RSV and HMPV neutralizing antibody responses.

Spatially Resolved Anisotropic Natural Abundance Deuterium 2D-NMR Spectroscopy Using Bimesophasic Lyotropic Chiral Systems.

In this paper, we describe, for the first time, the combined and original use of spatially resolved anisotropic natural abundance deuterium (ANAD) 2D-NMR experiments and bimesophasic lyotropic chiral systems to extract two independent sets of anisotropic parameters such as H-RQCs from a single NMR sample. As a pioneering example, we focus on a mixture of immiscible polypeptides (PBLG) and polyacetylene helical polymers (L-MSP) dissolved in weakly polar organic solvents (chloroform). Nondeuterated (D)-(+)-camphor is used as a model chiral solute.

Serotonin Syndrome Triggered by an Interaction Between Opioid Analgesics and Cobicistat: A Challenging Diagnostic Case Report.

Serotonin syndrome is a clinically diagnosed disorder that may occur secondary to medications that increase the release of endogenous serotonin, impair the reuptake of serotonin from the synaptic cleft, are direct serotonin receptor agonists, or increase the sensitivity of the postsynaptic serotonin receptor. In this case report, we describe the diagnosis of serotonin syndrome in a 60-year-old immunocompromised male. This case is unique, as many of the medications associated with the development of serotonin syndrome in this patient are not typically thought of as being associated with serotonin syndrome, though, in this clinical context, they combined to produce a profound pro-serotonergic effect.

Antiviral Activity of Active Materials: Standard and Finger-Pad-Based Innovative Experimental Approaches.

Environmental surfaces, including high-touch surfaces (HITS), bear a high risk of becoming fomites and can participate in viral dissemination through contact and transmission to other persons, due to the capacity of viruses to persist on such contaminated surface before being transferred to hands or other supports at sufficient concentration to initiate infection through direct contact. Interest in the development of self-decontaminating materials as additional safety measures towards preventing viral infectious disease transmission has been growing. Active materials are expected to reduce the viral charge on surfaces over time and consequently limit viral transmission capacity through direct contact.

Interactions Between Severe Acute Respiratory Syndrome Coronavirus 2 Replication and Major Respiratory Viruses in Human Nasal Epithelium.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with extensive nonpharmacological interventions, have profoundly altered the epidemiology of major respiratory viruses. Some studies have described virus-virus interactions, particularly manifested by viral interference mechanisms at different scales. However, our knowledge of the interactions between SARS-CoV-2 and other respiratory viruses remains incomplete.

Biotechnological production of sialylated solid lipid microparticles as inhibitors of influenza A virus infection.

Influenza viruses bind to their target through a multivalent interaction of their hemagglutinins (HAs) with sialosides at the host cell surface. To fight the virus, one therapeutic approach consists in developing sialylated multivalent structures that can saturate the virus HAs and prevent the binding to host cells. We describe herein the biotechnological production of sialylated solid lipid microparticles (SSLMs) in 3 steps: (i) a microbiological step leading to the large-scale production of sialylated maltodextrins by metabolic engineering of an Escherichia coli strain, (ii) a new in vitro glycosylation process using the amylomaltase MalQ, based on the transglycosylation of the terminal sialoside ligand of the sialylated maltodextrin onto a long-chain alkyl glucoside, and (iii) the formulation of the final SSLMs presenting a multivalent sialic acid.

Molnupiravir combined with different repurposed drugs further inhibits SARS-CoV-2 infection in human nasal epithelium in vitro.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with unprecedented economic and societal impact. Currently, several vaccines are available and multitudes of antiviral treatments have been proposed and tested. Although many of the vaccines show clinical efficacy, they are not equally accessible worldwide.

Avian Cell Line DuckCelt-T17 Is an Efficient Production System for Live-Attenuated Human Metapneumovirus Vaccine Candidate Metavac.

The development of a live-attenuated vaccine (LAV) for the prevention of human metapneumovirus (HMPV) infection is often hampered by the lack of highly efficient and scalable cell-based production systems that support eventual global vaccine production. Avian cell lines cultivated in suspension compete with traditional cell platforms used for viral vaccine manufacture. We investigated whether the DuckCelt-T17 avian cell line (Vaxxel), previously described as an efficient production system for several influenza strains, could also be used to produce a new HMPV LAV candidate (Metavac, SH gene-deleted A1/C-85473 HMPV).

Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs.

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses.

Transcriptional Profiling of Immune and Inflammatory Responses in the Context of SARS-CoV-2 Fungal Superinfection in a Human Airway Epithelial Model.

An increasing amount of evidence indicates a relatively high prevalence of superinfections associated with coronavirus disease 2019 (COVID-19), including invasive aspergillosis, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection, we determine and compare the host transcriptional response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus superinfection, using a model of reconstituted human airway epithelium. Our analyses reveal that both simple infection and superinfection induce strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection in the bronchial epithelial model compared to its nasal counterpart.

Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia.

In the current COVID-19 pandemic effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model.

The Prognostic Value of Quantitative EEG in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke.

Purpose: Previous work has shown that quantitative EEG measures correlate with the severity of ischemic stroke. This has not been systematically validated in patients with acute ischemic stroke who have undergone mechanical thrombectomy.

Methods: Data were collected from 73 patients who underwent mechanical thrombectomy and had a standard head set EEG performed during their hospital admission.

In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2.

In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.

Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues.

Like all obligate intracellular pathogens, influenza A virus (IAV) reprograms host cell's glucose and lipid metabolism to promote its own replication. However, the impact of influenza infection on white adipose tissue (WAT), a key tissue in the control of systemic energy homeostasis, has not been yet characterized. Here, we show that influenza infection induces alterations in whole-body glucose metabolism that persist long after the virus has been cleared.

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development.

Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen with currently no specific treatment or licensed vaccine. Different strategies to prevent this infection have been evaluated, including live-attenuated vaccines (LAV) based on SH and/or G protein deletions. This approach showed promising outcomes but has not been evaluated further using different viral strains.

Cortisol and Aldosterone Responses to Hypoglycemia and Na Depletion in Women With Non-Classic 21-Hydroxylase Deficiency.

Background: Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacologic challenges.

SPRi-based hemagglutinin quantitative assay for influenza vaccine production monitoring.

Influenza vaccine manufacturers lack tools, whatever the involved production bioprocess (egg or cell-based), to precisely and accurately evaluate vaccine antigen content from samples. Indeed, the gold standard single-radial immunodiffusion (SRID) assay, which remains the only validated assay for the evaluation of influenza vaccine potency, is criticized by the scientific community and regulatory agencies since a decade for its high variability, lack of flexibility and low sensitivity. We hereby report an imaging surface plasmon resonance (SPRi) assay for the quantification of both inactivated vaccine influenza antigens and viral particles derived from egg- and cell-based production samples, respectively.

Repurposing of Drugs as Novel Influenza Inhibitors From Clinical Gene Expression Infection Signatures.

Influenza virus infections remain a major and recurrent public health burden. The intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, highlight the critical need for novel therapeutic approaches. In this context, the aim of this study was to develop and validate an innovative strategy for drug repurposing as host-targeted inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase II clinical trials.

Influenza A viruses alter the stability and antiviral contribution of host E3-ubiquitin ligase Mdm2 during the time-course of infection.

The interplay between influenza A viruses (IAV) and the p53 pathway has been reported in several studies, highlighting the antiviral contribution of p53. Here, we investigated the impact of IAV on the E3-ubiquitin ligase Mdm2, a major regulator of p53, and observed that IAV targets Mdm2, notably via its non-structural protein (NS1), therefore altering Mdm2 stability, p53/Mdm2 interaction and regulatory loop during the time-course of infection. This study also highlights a new antiviral facet of Mdm2 possibly increasing the list of its many p53-independent functions.

Visually Significant Cystoid Macula Edema After Glaucoma Drainage Implant Surgery.

Purpose: This study examines the incidence of visually significant cystoid macular edema (CME) after glaucoma drainage implant (GDI) surgery and analyses risk factors associated with developing CME and prognosis with treatment.

Materials And Methods: In total, 185 eyes from 185 glaucoma patients (mean age, 72.46±13.