Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants.

Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed.

Conference Report: LPMHealthcare Emerging Viruses 2023 (EVOX23): Pandemics-Learning from the Past and Present to Prepare for the Future.

The emergence of SARS-CoV-2 has meant that pandemic preparedness has become a major focus of the global scientific community. Gathered in the historic St Edmund Hall college in Oxford, the one-day LPMHealthcare conference on emerging viruses (6 September 2023) sought to review and learn from past pandemics-the current SARS-CoV-2 pandemic and the Mpox outbreak-and then look towards potential future pandemics. This includes an emphasis on monitoring the "traditional" reservoirs of viruses with zoonotic potential, as well as possible new sources of spillover events, e.

Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants.

The accelerated development of the first generation COVID-19 vaccines has saved millions of lives, and potentially more from the long-term sequelae of SARS-CoV-2 infection. The most successful vaccine candidates have used the full-length SARS-CoV-2 spike protein as an immunogen. As expected of RNA viruses, new variants have evolved and quickly replaced the original wild-type SARS-CoV-2, leading to escape from natural infection or vaccine induced immunity provided by the original SARS-CoV-2 spike sequence.

Analysis of Antibody Neutralisation Activity against SARS-CoV-2 Variants and Seasonal Human Coronaviruses NL63, HKU1, and 229E Induced by Three Different COVID-19 Vaccine Platforms.

Coronaviruses infections, culminating in the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic beginning in 2019, have highlighted the importance of effective vaccines to induce an antibody response with cross-neutralizing activity. COVID-19 vaccines have been rapidly developed to reduce the burden of SARS-CoV-2 infections and disease severity. Cross-protection from seasonal human coronaviruses (hCoVs) infections has been hypothesized but is still controversial.

A Zn2+-triggered two-step mechanism of CLIC1 membrane insertion and activation into chloride channels.

The chloride intracellular channel (CLIC) protein family displays the unique feature of altering its structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, is found in the cytoplasm or in internal and plasma membranes, with membrane relocalisation linked to endothelial disfunction, tumour proliferation and metastasis. The molecular switch promoting CLIC1 activation remains under investigation.

Different decay of antibody response and VOC sensitivity in naïve and previously infected subjects at 15 weeks following vaccination with BNT162b2.

Background: COVID-19 vaccines have demonstrated effectiveness in reducing SARS-CoV-2 mild and severe outcomes. In vaccinated subjects with SARS-CoV-2 history, RBD-specific IgG and pseudovirus neutralization titers were rapidly recalled by a single BTN162b2 vaccine dose to higher levels than those in naïve recipients after the second dose, irrespective of waning immunity. In this study, we inspected the long-term kinetic and neutralizing responses of S-specific IgG induced by two administrations of BTN162b2 vaccine in infection-naïve subjects and in subjects previously infected with SARS-CoV-2.

Cross-Cultural Adaptation and Reliability Testing of Chinese Version of the Living with Medicines Questionnaire in Elderly Patients with Chronic Diseases.

Background: The Living with Medicines Questionnaire (LMQ-3) is a reliable, valid instrument used to assess the medication-related burden of patients with chronic disease using long-term medication, but it has not been used in China.

Purpose: To translate and cross-culturally adapt the LMQ-3 into Chinese and assess its reliability and validity among elderly patients with chronic disease.

Methods: After translation and back-translation, views from an expert group and cognitive interviews with elderly persons using multiple medicines were used to ensure the cultural relevance of the LMQ-3.

Characterisation of SARS-CoV-2 Lentiviral Pseudotypes and Correlation between Pseudotype-Based Neutralisation Assays and Live Virus-Based Micro Neutralisation Assays.

The recent outbreak of a novel Coronavirus (SARS-CoV-2) and its rapid spread across the continents has generated an urgent need for assays to detect the neutralising activity of human sera or human monoclonal antibodies against SARS-CoV-2 spike protein and to evaluate the serological immunity in humans. Since the accessibility of live virus microneutralisation (MN) assays with SARS-CoV-2 is limited and requires enhanced bio-containment, the approach based on "pseudotyping" can be considered a useful complement to other serological assays. After fully characterising lentiviral pseudotypes bearing the SARS-CoV-2 spike protein, we employed them in pseudotype-based neutralisation assays in order to profile the neutralising activity of human serum samples from an Italian sero-epidemiological study.

Protection From Influenza by Intramuscular Gene Vector Delivery of a Broadly Neutralizing Nanobody Does Not Depend on Antibody Dependent Cellular Cytotoxicity.

Cross-subtype neutralizing single domain antibodies against influenza present new opportunities for immunoprophylaxis and pandemic preparedness. Their simple modular structure and single open reading frame format are highly amenable to gene therapy-mediated delivery. We have previously described R1a-B6, an alpaca-derived single domain antibody (nanobody), that is capable of potent cross-subtype neutralization of H1N1, H5N1, H2N2, and H9N2 influenza viruses, through binding to a highly conserved epitope in the influenza hemagglutinin stem region.

Nonsteroidal anti-inflammatory drugs alter vasa recta diameter via pericytes.

We have previously shown that vasa recta pericytes are known to dilate vasa recta capillaries in the presence of PGE2 and contract vasa recta capillaries when endogenous production of PGE2 is inhibited by the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin. In the present study, we used a live rat kidney slice model to build on these initial observations and provide novel data that demonstrate that nonselective, cyclooxygenase-1-selective, and cyclooxygenase -2-selective NSAIDs act via medullary pericytes to elicit a reduction of vasa recta diameter. Real-time images of in situ vasa recta were recorded, and vasa recta diameters at pericyte and nonpericyte sites were measured offline.

Urinary ATP as an indicator of infection and inflammation of the urinary tract in patients with lower urinary tract symptoms.

Background: Adenosine-5'-triphosphate (ATP) is a neurotransmitter and inflammatory cytokine implicated in the pathophysiology of lower urinary tract disease. ATP additionally reflects microbial biomass thus has potential as a surrogate marker of urinary tract infection (UTI). The optimum clinical sampling method for ATP urinalysis has not been established.

The evolving role of renal pericytes.

Purpose Of Review: The purpose of this review is to focus on the most recent developments in our understanding of the physiological and pathophysiological role(s) that renal pericytes play in the kidney. We will highlight the most important and interesting advances made in the last 12 months and aim to provide a concise summary of the exciting progress in this field.

Recent Findings: Pericytes have increasingly been the subject of much interest in the renal field, with particular attention focusing on their key role as regulators of medullary blood flow (MBF), their ability to coordinate tubular and vascular function via tubulovascular cross-talk mechanisms, and most recently, their role in the pathogenesis of renal diseases such as fibrosis and associated forms of chronic disease.

Fluorescence imaging of intracellular calcium signals in intact kidney tissue.

Background: Intracellular calcium (Ca(2+)) plays an important role in normal renal physiology and in the pathogenesis of various kidney diseases; however, the study of Ca(2+) signals in intact tissue has been limited by technical difficulties, including achieving adequate loading of Ca(2+)-sensitive fluorescent dyes. The kidney slice preparation represents a model whereby three-dimensional tissue architecture is preserved and structures in both the cortex and medulla can be imaged using confocal or multiphoton microscopy.

Methods: Ca(2+)-sensitive dyes Rhod-2, Fura-red and Fluo-4 were loaded into tubular and vascular cells in rat kidney slices using a re-circulating perfusion system and real-time imaging of Ca(2+) signals was recorded by confocal microscopy.

An intact kidney slice model to investigate vasa recta properties and function in situ.

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ.

Dominant negative effects of a non-conducting TREK1 splice variant expressed in brain.

Two-pore domain potassium (K(2P)) channels modulate neuronal excitability throughout the entire CNS. The stretch-activated channel TREK1 (K(2P)2.1) is expressed widely in brain and has been linked to depression, neuroprotection, pain perception, and epilepsy.

Therapeutic potential of neuronal two-pore domain potassium-channel modulators.

Two-pore domain potassium (K2P) channels are expressed in cells throughout the body and give rise to leak potassium currents which control the excitability of these cells. Although not inhibited by classical potassium channel-blocking drugs, such as tetraethylammonium and 4-aminopyridine, K2P channels are regulated by a diverse array of pharmacological mediators. There are six main families of K2P channels and among these certain members of the TREK family (ie, TREK-1 and TREK-2) are activated by general anesthetic agents such as halothane, xenon and nitrous oxide.

Potential of cationic porphyrins for photodynamic treatment of cutaneous Leishmaniasis.

Four tetracationic porphyrins have been investigated for their ability to photo-inactivate Leishmania major promastigotes. Parallel photocytotoxicity assays against keratinocytes and macrophages show significant differences in activity between the microorganism and mammalian cells. Results suggest that it may be possible to photodynamically inactivate macrophages infected with Leishmania and the promastigote form of the microorganism, while minimising damage to surrounding tissue.