Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global COVID-19 pandemic. One possibility to control the pandemic is to induce sterilizing immunity through the induction and maintenance of neutralizing antibodies preventing SARS-CoV-2 from entering human cells to replicate in. METHODS: We report the construction and in vitro and in vivo characterization of a SARS-CoV-2 subunit vaccine (PreS-RBD) based on a structurally folded recombinant fusion protein consisting of two SARS-CoV-2 Spike protein receptor-binding domains (RBD) fused to the N- and C-terminus of hepatitis B virus (HBV) surface antigen PreS to enable the two unrelated proteins serving as immunologic carriers for each other. RESULTS: PreS-RBD, but not RBD alone, induced a robust and uniform RBD-specific IgG response in rabbits. Currently available genetic SARS-CoV-2 vaccines induce mainly transient IgG1 responses in vaccinated subjects whereas the PreS-RBD vaccine induced RBD-specific IgG antibodies consisting of an early IgG1 and sustained IgG4 antibody response in a SARS-CoV-2 naive subject. PreS-RBD-specific IgG antibodies were detected in serum and mucosal secretions, reacted with SARS-CoV-2 variants, including the omicron variant of concern and the HBV receptor-binding sites on PreS of currently known HBV genotypes. PreS-RBD-specific antibodies of the immunized subject more potently inhibited the interaction of RBD with its human receptor ACE2 and their virus-neutralizing titers (VNTs) were higher than median VNTs in a random sample of healthy subjects fully immunized with registered SARS-CoV-2 vaccines or in COVID-19 convalescent subjects. CONCLUSION: The PreS-RBD vaccine has the potential to serve as a combination vaccine for inducing sterilizing immunity against SARS-CoV-2 and HBV by stopping viral replication through the inhibition of cellular virus entry.

Modified ABCDEF-Bundles for Critically Ill Pediatric Patients - What Could They Look Like?

Background and Significance: Advances in pediatric intensive care have led to markedly improved survival rates in critically ill children. Approximately 70% of those children survive with varying forms of complex chronic diseases or impairment/disabilities. Length of stay, length of mechanical ventilation and number of interventions per patient are increasing with rising complexity of underlying diseases, leading to increasing pain, agitation, withdrawal symptoms, delirium, immobility, and sleep disruption. The ICU-Liberation Collaborative of the Society of Critical Care Medicine has developed a number of preventative measures for prevention, early detection, or treatment of physical and psychiatric/psychological sequelae of oftentimes traumatic intensive care medicine. These so called ABCDEF-Bundles consist of elements for (A) assessment, prevention and management of pain, (B) spontaneous awakening and breathing trials (SAT/SBT), (C) choice of analgesia and sedation, (D) assessment, prevention and management of delirium, (E) early mobility and exercise and (F) family engagement and empowerment. For adult patients in critical care medicine, research shows significant effects of bundle-implementation on survival, mechanical ventilation, coma, delirium and post-ICU discharge disposition. Research regarding PICS in children and possible preventative or therapeutic intervention is insufficient as yet. This narrative review provides available information for modification and further research on the ABCDEF-Bundles for use in critically ill children. Material and Methods: A narrative review of existing literature was used. Results: One obvious distinction to adult patients is the wide range of different developmental stages of children and the even closer relationship between patient and family. Evidence for pediatric ABCDEF-Bundles is insufficient and input can only be collected from literature regarding different subsections and topics. Conclusion: In addition to efforts to improve analgesia, sedation and weaning protocols with the aim of prevention, early detection and effective treatment of withdrawal symptoms or delirium, efforts are focused on adjusting ABCDEF bundle for the entire pediatric age group and on strengthening families' decision-making power, understanding parents as a resource for their child and involving them early in the care of their children.

Ultrahigh-resolution OCT imaging of the human cornea.

We present imaging of corneal pathologies using optical coherence tomography (OCT) with high resolution. To this end, an ultrahigh-resolution spectral domain OCT (UHR-OCT) system based on a broad bandwidth Ti:sapphire laser is employed. With a central wavelength of 800 nm, the imaging device allows to acquire OCT data at the central, paracentral and peripheral cornea as well as the limbal region with 1.2 µm x 20 µm (axial x lateral) resolution at a rate of 140 000 A-scans/s. Structures of the anterior segment of the eye, not accessible with commercial OCT systems, are visualized. These include corneal nerves, limbal palisades of Vogt as well as several corneal pathologies. Cases such as keratoconus and Fuchs's endothelial dystrophy as well as infectious changes caused by diseases like Acanthamoeba keratitis and scarring after herpetic keratitis are presented. We also demonstrate the applicability of our system to visualize epithelial erosion and intracorneal foreign body after corneal trauma as well as chemical burns. Finally, results after Descemet's membrane endothelial keratoplasty (DMEK) are imaged. These clinical cases show the potential of UHR-OCT to help in clinical decision-making and follow-up. Our results and experience indicate that UHR-OCT of the cornea is a promising technique for the use in clinical practice, but can also help to gain novel insight in the physiology and pathophysiology of the human cornea.

Effect of different lubricant eye gels on tear film thickness as measured with ultrahigh-resolution optical coherence tomography.

PURPOSE: To compare the effect of a single drop of different lubricant eye gels on tear film thickness (TFT) as measured with ultrahigh-resolution optical coherence tomography (UHR-OCT) in patients with mild-to-moderate dry eye disease (DED). METHODS: The study followed a randomized, single-masked, observer-blinded parallel group design. Patients received a single dose of either unpreserved trehalose 3% + hyaluronic acid 0.15% (TH), hyaluronic acid 0.2% (HA) or polyethylene glycol 0.4% + propylene glycol 0.3% (PP) eye drops. In total, 60 patients were included and TFT was measured using a custom-built UHR-OCT system. RESULTS: The mean TFT at baseline was 3.5 ± 0.7 µm. There was a significant difference in the time-course of TFT between the three groups (p = 0.001 between groups). Ten minutes after instillation, TFT increased by 155.8 ± 86.6%, 65.7 ± 71.5% and 33.4 ± 19.6% in the PP, TH and HA group, respectively (p < 0.001 between groups). Thirty minutes after instillation, the effect of all three different agents on TFT was comparable. Sixty and 120 min after administration, a significant increase in TFT was only seen for the TH group, but not for the other products (60 min: p < 0.021 between groups; 120 min: p < 0.037 between groups). CONCLUSION: In conclusion, we observed differences in TFT after administration of the lubricant gels. Ten minutes after instillation, a pronounced increase in TFT was observed in all groups. As compared to the other products, the combination of trehalose 3% + hyaluronic acid 0.15% offers a significantly longer increase in TFT indicating for a longer residence time.