Monovalent and trivalent VSV-based COVID-19 vaccines elicit neutralizing antibodies and CD8 T cells against SARS-CoV-2 variants.

Recombinant vesicular stomatitis virus (rVSV) vaccines expressing spike proteins of Wuhan, Beta, and/or Delta variants of SARS-CoV-2 were generated and tested for induction of antibody and T cell immune responses following intramuscular delivery to mice. rVSV-Wuhan and rVSV-Delta vaccines and an rVSV-Trivalent (mixed rVSV-Wuhan, -Beta, -Delta) vaccine elicited potent neutralizing antibodies (nAbs) against live SARS-CoV-2 Wuhan (USAWA1), Beta (B.1.

Pre-Germinal Center Interactions with T Cells Are Natural Checkpoints to Limit Autoimmune B Cell Responses.

Interactions with Ag-specific T cells drive B cell activation and fate choices that ultimately determine the quality of high-affinity Ab responses. As such, these interactions, and especially the long-lived interactions that occur before germinal center formation, may be important checkpoints to regulate undesirable responses. Using mouse model Ag systems, we directly observed interactions between T and B cells responding to the self-antigen myelin oligodendrocyte glycoprotein (MOG) and found that they are of lower quality compared with interactions between cells responding to the model foreign Ag nitrophenyl-haptenated OVA.

Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial.

Background: Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease.

Objective: We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability.

Methods: Nine patients with MS were recruited and provided monthly FMTs for up to six months.

Autoreactive, Low-Affinity T Cells Preferentially Drive Differentiation of Short-Lived Memory B Cells at the Expense of Germinal Center Maintenance.

B cell fate decisions within a germinal center (GC) are critical to determining the outcome of the immune response to a given antigen. Here, we characterize GC kinetics and B cell fate choices in a response to the autoantigen myelin oligodendrocyte glycoprotein (MOG) and compare the response with a standard model foreign antigen. Both antigens generate productive primary responses, as evidenced by GC development, circulating antigen-specific antibodies, and differentiation of memory B cells.

Local Sphingosine Kinase 1 Activity Improves Islet Transplantation.

Pancreatic islet transplantation is a promising clinical treatment for type 1 diabetes, but success is limited by extensive β-cell death in the immediate posttransplant period and impaired islet function in the longer term. Following transplantation, appropriate vascular remodeling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase (SK) pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown.

A non-canonical role for desmoglein-2 in endothelial cells: implications for neoangiogenesis.

Desmogleins (DSG) are a family of cadherin adhesion proteins that were first identified in desmosomes and provide cardiomyocytes and epithelial cells with the junctional stability to tolerate mechanical stress. However, one member of this family, DSG2, is emerging as a protein with additional biological functions on a broader range of cells. Here we reveal that DSG2 is expressed by non-desmosome-forming human endothelial progenitor cells as well as their mature counterparts [endothelial cells (ECs)] in human tissue from healthy individuals and cancer patients.

Sphingosine 1-phosphate is a ligand for peroxisome proliferator-activated receptor-γ that regulates neoangiogenesis.

Sphingosine 1-phosphate (S1P) is a bioactive lipid that can function both extracellularly and intracellularly to mediate a variety of cellular processes. Using lipid affinity matrices and a radiolabeled lipid binding assay, we reveal that S1P directly interacts with the transcription factor peroxisome proliferator-activated receptor (PPAR)γ. Herein, we show that S1P treatment of human endothelial cells (ECs) activated a luciferase-tagged PPARγ-specific gene reporter by ∼12-fold, independent of the S1P receptors.

Interleukin-3 greatly expands non-adherent endothelial forming cells with pro-angiogenic properties.

Circulating endothelial progenitor cells (EPCs) provide revascularisation for cardiovascular disease and the expansion of these cells opens up the possibility of their use as a cell therapy. Herein we show that interleukin-3 (IL3) strongly expands a population of human non-adherent endothelial forming cells (EXnaEFCs) with low immunogenicity as well as pro-angiogenic capabilities in vivo, making their therapeutic utilisation a realistic option. Non-adherent CD133(+) EFCs isolated from human umbilical cord blood and cultured under different conditions were maximally expanded by day 12 in the presence of IL3 at which time a 350-fold increase in cell number was obtained.

Over-expression of sphingosine kinase-1 enhances a progenitor phenotype in human endothelial cells.

Objectives: The use of endothelial progenitor cells in vascular therapies has been limited due to their low numbers present in the bone marrow and peripheral blood. The aim of this study was to investigate the effect of sphingosine kinase on the de-differentiation of mature human endothelial cells toward a progenitor phenotype.

Methods: The lipid enzyme sphingosine kinase-1 was lentivirally over-expressed in human umbilical vein endothelial cells and cells were analyzed for progenitor phenotype and function.