AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans.

Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4 T cell and memory B cell responses.

Medical management of obesity.

Obesity is a global epidemic that has worsened over the past few decades. It is strongly associated with multiple health conditions, including type 2 diabetes mellitus, cardiovascular diseases, obstructive sleep apnoea, certain malignancies and has an increased mortality risk. The annual cost of obesity to the NHS is around £6 billion, projected to increase to just under £10 billion by 2050.

CD8 T cell differentiation status correlates with the feasibility of sustained unresponsiveness following oral immunotherapy.

While food allergy oral immunotherapy (OIT) can provide safe and effective desensitization (DS), the immune mechanisms underlying development of sustained unresponsiveness (SU) following a period of avoidance are largely unknown. Here, we compare high dimensional phenotypes of innate and adaptive immune cell subsets of participants in a previously reported, phase 2 randomized, controlled, peanut OIT trial who achieved SU vs. DS (no vs.

Systems vaccinology of the BNT162b2 mRNA vaccine in humans.

The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2).

Systems biological assessment of human immunity to BNT162b2 mRNA vaccination.

The emergency use authorization of two COVID-19 mRNA vaccines in less than a year since the emergence of SARS-CoV-2, represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems biological approach to comprehensively profile the innate and adaptive immune responses in 56 healthy volunteers vaccinated with the Pfizer-BioNTech mRNA vaccine.

Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab.

Background: Multifood oral immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, XOLAIR ) treatment affords safe, effective, and rapid desensitization to multiple foods, although the specific immune mechanisms mediating this desensitization remain to be fully elucidated.

Methods: Participants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the immune profile of PBMCs and plasma taken at baseline, week 8, and week 36 using high-dimensional mass cytometry, component-resolved diagnostics, the indirect basophil activation test, and Luminex.

Utilizing a Behavioral Health Bundle to Improve Patient and Clinician Safety for Hospitalized Children.

Unlabelled: Due to limited psychiatric hospital availability, increasing numbers of pediatric patients with behavioral health (BH) needs are hospitalized in medical units in the US Patients and staff are at increased risk for safety events like self-harm or aggression. Our study aimed to decrease safety events by 25% over a year among hospitalized children with BH diagnoses by implementing an intervention bundle.

Methods: A multidisciplinary team developed and implemented a BH intervention bundle that included a BH equipment cart, an electronic medical record tool for BH patient identification/stratification, a de-escalation team, daily operational BH phone call, and staff training with a safety checklist.

A Quality Improvement Initiative To Improve Postdischarge Antimicrobial Adherence.

Objectives: Bedside delivery of discharge medications improves caregiver understanding and experience. Less is known about its impact on medication adherence. We aimed to improve antimicrobial adherence by increasing on-time first home doses for patients discharged from the pediatric hospital medicine service from 33% to 80% over 1 year via creation of a discharge medication delivery and counseling "Meds to Beds" (M2B) program.

Transcriptional changes in peanut-specific CD4+ T cells over the course of oral immunotherapy.

Oral immunotherapy (OIT) can successfully desensitize allergic individuals to offending foods such as peanut. Our recent clinical trial (NCT02103270) of peanut OIT allowed us to monitor peanut-specific CD4+ T cells, using MHC-peptide Dextramers, over the course of OIT. We used a single-cell targeted RNAseq assay to analyze these cells at 0, 12, 24, 52, and 104 weeks of OIT.

Immune Checkpoint Function of CD85j in CD8 T Cell Differentiation and Aging.

Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging.

Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis.

Background: Basophil activation tests (BATs) have promise for research and for clinical monitoring of patients with allergies. However, BAT protocols vary in blood anticoagulant used and temperature and time of storage before testing, complicating comparisons of results from various studies.

Objective: We attempted to establish a BAT protocol that would permit analysis of blood within 24 hours of obtaining the sample.

Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.

Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls.

Intracellular Cytokine Staining (ICS) on Human Lymphocytes or Peripheral Blood Mononuclear Cells (PBMCs).

Production of cytokines plays an important role in the immune response. Cytokines are involved in many different pathways including the induction of many anti-viral proteins by IFN gamma, the induction of T cell proliferation by IL-2 and the inhibition of viral gene expression and replication by TNF alpha. Cytokines are not preformed factors but are rapidly produced and secreted in response to cellular activation.

Intracellular Cytokine Staining on PBMCs Using CyTOF™ Mass Cytometry.

In this protocol, we use a CyTOF™ mass cytometry to collect single-cell data on a large number of cytokines/chemokines as well as cell-surface proteins that characterize T cells and other immune cells. The current selected mass window in AW 103-203 includes the lanthanides used for most antibody labeling, along with iridium and rhodium for DNA intercalators. The output data are in the format as .

Immunodominant T-cell epitopes of MOG reside in its transmembrane and cytoplasmic domains in EAE.

Objective: Studies evaluating T-cell recognition of myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE), have focused mostly on its 117 amino acid (aa) extracellular domain, especially peptide (p) 35-55. We characterized T-cell responses to the entire 218 aa MOG sequence, including its transmembrane and cytoplasmic domains.

Methods: T-cell recognition in mice was examined using overlapping peptides and intact full-length mouse MOG.

A review of current treatment strategies for restless legs syndrome (Willis-Ekbom disease).

Restless legs syndrome (RLS), recently renamed Willis-Ekbom disease (WED), is a common movement disorder. It is characterised by the need to move mainly the legs due to uncomfortable, sometimes painful sensations in the legs, which have a diurnal variation and a release with movement. Management is complex.