Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire.

The generation of broadly neutralizing antibodies (bnAbs) to specific HIV epitopes of the HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The current animal models we use have been unable to reliable produce a broadly neutralizing antibody response, with the exception of cows. Cows have rapidly and reliably produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer.

Validation of the NUT CRACKER Diagnostic Algorithm and Prediction for Cashew and Pistachio Co-Allergy.

Background: Because of the high cross-sensitization among tree nuts, the NUT CRACKER (Nut Co-reactivity-Acquiring Knowledge for Elimination Recommendations) study proposed a diagnostic algorithm to minimize the number of required oral food challenges (OFCs).

Objective: To validate the algorithm for cashew and pistachio allergy and determine markers for allergic severity.

Methods: Patients (n = 125) with a median age of 7.

Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.

Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development and have suggested a role for superinfection as a potential enhancer of neutralization breadth. Here we describe the development of a potent bnAb lineage that was elicited by two founder viruses to inform vaccine design.

Highly mutated antibodies capable of neutralizing N276 glycan-deficient HIV after a single immunization with an Env trimer.

Elicitation of HIV broadly neutralizing antibodies (bnAbs) is challenging because unmutated bnAb precursors are rare and seldom bind HIV envelope glycoprotein (Env) trimers. One strategy to initiate bnAb responses is to use germline-targeting (GT) immunogens with high affinity to bnAb-class precursor B cells and then shepherd affinity maturation with booster immunogens that successively look more like native Env. In a mouse model where the frequency of VRC01-precursor (VRC01) B cells mimics that of humans, we show that following a GT HIV Env trimer protein prime, VRC01-class B cells in the germinal center (GC) acquire high-affinity VRC01-class B cell somatic hypermutations (SHMs).

Cashew oral immunotherapy for desensitizing cashew-pistachio allergy (NUT CRACKER study).

Background: Oral immunotherapy (OIT) is a treatment option for patients with milk, egg, and peanut allergy, but data on the efficacy and safety of cashew OIT are limited.

Methods: A cohort of 50 cashew-allergic patients aged ≥4 years, who were consecutively enrolled into cashew OIT (target dose 4000 mg protein) between 4/2016 and 12/2019. Fifteen cashew-allergic patients who continued cashew elimination served as observational controls.

Coronary atherosclerosis severity is closely associated with decreased GLP-1R positivity among CD16 pro-inflammatory and patrolling monocyte subsets.

Background And Aims: Glucagon Like Peptide-1 Receptor (GLP-1R) activation reduces pro-inflammatory responses of human monocytes, their accumulation in the vascular wall and foam cell formation inhibiting atherosclerogenesis. This suggests that reduction of circulating GLP-1-1R positive monocytes may have pro-atherogenic effects. It is unknown whether different CD14/CD16 monocytes subsets display GLP-1R and whether their relative proportions correlate with atherosclerosis severity.

Combinatorial advantage of Ses i 1-specific IgE and basophil activation for diagnosis of sesame food allergy.

Background: The prevalence of sesame food allergy (SFA) is increasing worldwide with the potential of anaphylactic reactions upon exposure. Utility of specific component IgE testing as an alternative to the oral food challenge (OFC), the diagnostic standard, is being investigated.

Methods: Patients (n = 42) with suspected SFA completed an open OFC to sesame.

Microbial signature in IgE-mediated food allergies.

Background: Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state.

Methods: To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed.

A Prospective Validation of the NUT CRACKER Diagnostic Algorithm for Walnut and Pecan Allergy with Prediction of Severity.

Background: We previously devised an algorithm using skin prick tests (SPT), basophil activation tests (BAT), and co-allergy status to reduce the need for oral food challenges (OFCs) in 63 patients with suspected walnut/pecan allergies.

Objective: To validate prospectively the NUT CRACKER (Nut Co-Reactivity-Acquiring Knowledge for Elimination Recommendations) diagnostic algorithm in a new cohort of patients (n = 120) and to study the utility of SPT and BAT in predicting walnut-pecan allergy severity in both groups (n = 183).

Methods: Patients (n = 183) aged 8 (6-11) years, median (interquartile range), with suspected tree nut allergy were studied.

Clinical and Molecular Characterization of Walnut and Pecan Allergy (NUT CRACKER Study).

Background: Diagnostic methods for distinguishing walnut-allergic patients from walnut-sensitized but walnut-tolerant individuals are limited. Furthermore, characteristics of single walnut versus dual walnut-pecan allergy are lacking.

Objective: To provide clinical and molecular characteristics of walnut- and pecan-allergic patients.

Efficacy and Safety of Sesame Oral Immunotherapy-A Real-World, Single-Center Study.

Background: The presence of sesame in Western diet is increasing, making its avoidance by sesame-allergic patients more challenging.

Objective: To report the efficacy and safety of sesame oral immunotherapy (OIT).

Methods: Sixty patients aged 4 years or older, diagnosed as sesame-allergic on the basis of a positive oral food challenge, were consecutively enrolled into OIT between November 2014 and November 2017.

Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study.

Background: The safety and efficacy of oral immunotherapy for tree nut allergy has not been demonstrated to date, and its effectiveness is complicated by the high prevalence of co-allergies to several nuts. This study aimed to investigate the use of walnut oral immunotherapy in the desensitisation of walnut and additional tree nuts in patients who are co-allergic to several nuts.

Methods: In a single-centre, prospective cohort study (the Nut Co-Reactivity ACquiring Knowledge for Elimination Recommendations study) at the Institute of Allergy, Immunology, and Paediatric Pulmonology at the Yitzhak Shamir Medical Centre, we recruited patients aged 4 years or older who were allergic to walnut, with or without co-allergy to pecan, hazelnut, and cashew.

Phospholipase C-Gamma 2 Activity in Familial Steroid-Sensitive Nephrotic Syndrome.

Background: Familial Steroid-sensitive Nephrotic Syndrome (SSNS) is rare, complicating the identification of candidate genes. A recent population-based approach study of SSNS identified HLA-DQA1 and Phospholipase C-Gamma 2 (PLCG2) missense coding variants as candidate loci. PLCG2 is a signaling molecule regulated by phosphorylation and is critical for Ca flux in cells of the immune system.

Food allergy to previously tolerated foods: Course and patient characteristics.

Background: The acquisition of food allergy (FA) to previously safely consumed basic food proteins is an unusual presentation of immunoglobulin E (IgE)-mediated allergic disease.

Objective: We sought to characterize patients who developed FA to previously tolerated foods (FA-PTF), including underlying reasons for and length of elimination diet of previously tolerated foods.

Methods: Patients (n = 30) with complaints consistent with FA to foods previously consumed safely were evaluated.

Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients.

Background: Patients with IgE-mediated cow's milk allergy who are nonreactive to baked milk (BM) can be desensitized with BM to promote tolerance to unheated milk (UM).

Objective: We sought to test whether patients who are BM reactive can progress in BM oral immunotherapy (OIT) and become desensitized to UM as well.

Methods: Fifteen patients (>4 years) who previously failed to complete our milk OIT program were enrolled into the BM OIT protocol.

Association with soil bacteria enhances p38-dependent infection resistance in Caenorhabditis elegans.

The importance of our inner microbial communities for proper immune responses against invading pathogens is now well accepted, but the mechanisms underlying this protection are largely unknown. In this study, we used Caenorhabditis elegans to investigate such mechanisms. Since very little is known about the microbes interacting with C.

Dimerization of NKp46 receptor is essential for NKp46-mediated lysis: characterization of the dimerization site by epitope mapping.

NKp46 is a primary activating receptor of NK cells that is involved in lysis of target cells by NK cells. Previous studies showed that the membrane-proximal domain of NKp46 (NKp46D2) retained the binding of NKp46 to its ligands and is involved in lysis. We studied NKp46D2 by using a peptide-based epitope mapping approach and identified an NKp46D2-derived linear epitope that inhibited NKp46-mediated lysis.

Human NK cell recognition of target cells in the prism of natural cytotoxicity receptors and their ligands.

The matter of the pathogen- and cancer-associated ligands recognized by the Natural Cytotoxicity Receptors (NCRs) has been a subject of intense research ever since the identification of the NCRs more than 12 years ago by Alessandro and Lorenzo Moretta: NKp46 in 1997, NKp44 in 1998, and finally NKp30 in 1999. Expression patterns recognized by NCRs include pathogen-derived, pathogen-induced, and cancer-associated cellular 'self' ligands. Pathogen-exposed cells may exhibit both types of pathogen-associated ligands.

Upregulation of MHC class I expression following dengue virus infection: the mechanism at the promoter level.

Unlike many other viruses that downregulate MHC class I expression on infected cell membranes, flaviviruses were reported to upregulate the MHC class I expression. Dengue virus was shown to induce HLA class I expression; however, the precise transcriptional mechanism that is used by the virus remains unclear. This article assessed the findings of a recently published report describing the mechanism used by dengue virus to induce HLA-A2 expression and characterizing the transcription factors that are involved.