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The abundances of migratory shark species observed throughout the Mid-Atlantic Bight (MAB) during productive summer months suggest that this region provides critical habitat and prey resources to these taxa. However, the principal prey assemblages sustaining migratory shark biomass in this region are poorly defined. We applied high-throughput DNA metabarcoding to shark feces derived from cloacal swabs across nine species of Carcharhinid and Lamnid sharks to (1) quantify the contribution of broad taxa (e.g., invertebrates, fishes) supporting shark biomass during seasonal residency in the MAB and (2) determine whether the species displayed distinct dietary preference indicative of resource partitioning. DNA metabarcoding resulted in high taxonomic (species-level) resolution of shark diets with actinopterygian and elasmobranch fishes as the dominant prey categories across the species. DNA metabarcoding identified several key prey groups consistent across shark taxa that are likely integral for sustaining their biomass in this region, including Atlantic menhaden (Brevoortia tyrannus), Atlantic mackerel (Scomber scombrus), and benthic elasmobranchs, including skates. Our results are consistent with previously published stomach content data for the shark species of similar size range in the Northwest Atlantic Ocean, supporting the efficacy of cloacal swab DNA metabarcoding as a minimally invasive diet reconstruction technique. The high reliance of several shark species on Atlantic menhaden could imply wasp-waist food-web conditions during the summer months, whereby high abundances of forage fishes sustain a diverse suite of migratory sharks within a complex, seasonal food web., (© 2023 Fisheries Society of the British Isles.)

Monoclonal antibodies against tumor necrosis factor-alpha (TNFα) are widely used for treatment of inflammatory diseases. However, despite the inhibitory effect this class of drugs has on the immune system, anti-drug antibodies are often formed with continuous use. Particles formed during stress conditions, which can be used to simulate storage and handling conditions of commercial antibodies, have previously been associated with the formation of anti-drug antibodies. This study investigates the relationship between particles, oligomerization, folding and chemical degradation on the in vitro cytokine response toward the TNFα inhibitor adalimumab. Adalimumab aggregates generated using stir and heat stress were fractionated into distinct sub-populations, and their structure and immunogenic potential were evaluated. A chemically degraded sample of adalimumab was included to compare particle composition with the milder accelerated heat and stir stressed conditions. Particles from stressed adalimumab samples induced elevated cytokine levels and CD4+ T cell proliferation in vitro compared to non-stressed samples. Samples enriched with both submicron and subvisible particles of adalimumab induced the strongest cytokine release and the strongest CD4+ T cell proliferation despite maintaining some TNFα inhibitory functionality. Samples that were stressed and subsequently purified of subvisible and submicron particles did not elicit a significantly higher cytokine response or show increased CD4+ T cell proliferation compared to a non-stressed sample. Oxidation-induced chemical modifications in adalimumab, mainly in Met, His, Trp, and Tyr, were not found to be sufficient in absence of particle formation to induce increased CD4+ T cell proliferation or cytokine release despite less decreased TNFα inhibitory activity of adalimumab. These observations provide further evidence that particles do indeed potentiate the immunogenic potential of adalimumab., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

As immunological selection for escape mutants continues to give rise to future SARS-CoV-2 variants, novel universal therapeutic strategies against ACE2-dependent viruses are needed. Here we present an IgM-based decavalent ACE2 decoy that has variant-agnostic efficacy. In immuno-, pseudovirus, and live virus assays, IgM ACE2 decoy had potency comparable or superior to leading SARS-CoV-2 IgG-based mAb therapeutics evaluated in the clinic, which were variant-sensitive in their potency. We found that increased ACE2 valency translated into increased apparent affinity for spike protein and superior potency in biological assays when decavalent IgM ACE2 was compared to tetravalent, bivalent, and monovalent ACE2 decoys. Furthermore, a single intranasal dose of IgM ACE2 decoy at 1 mg/kg conferred therapeutic benefit against SARS-CoV-2 Delta variant infection in a hamster model. Taken together, this engineered IgM ACE2 decoy represents a SARS-CoV-2 variant-agnostic therapeutic that leverages avidity to drive enhanced target binding, viral neutralization, and in vivo respiratory protection against SARS-CoV-2.

Research has documented the need for mental health services among refugee and immigrant youth. A joint collaboration on a community-based participatory research (CBPR) research project between a university, a local art and health collective, and an immigrant and refugee organization sought to identify and understand the mental health needs and strategies for immigrant youth in Philadelphia through youth discussion and engagement in a variety of art workshops. As a result of the COVID-19 pandemic, this CBPR research project was forced to make several programmatic changes, such as shifting to a virtual setting, that impacted project implementation and intended outcomes. These changes highlight valuable lessons and practical implications in pivoting a program during COVID-19 to continue working with marginalized communities with limited resources, including barriers to technology access, at a time when effectively addressing mental health for immigrant youth has become both more challenging and pressing.

Among patients that receive Remicade® therapy, more than 20% have adverse infusion related reactions and approximately 50% have immunogenic responses. 1-3 Upon characterization of initial Remicade®-IV solution we observed a high concentration of subvisible particles that could inadvertently be delivered to patients. This solution was processed through the IV infusion system, mimicking the typical clinical administration setup - either with or without an in-line filter connected to the IV line. The samples generated thereafter were tested using various in vitro assays for activation of the innate immune system via cytokine release in whole blood and in peripheral blood mononuclear cell (PBMC) cultures, and activation of the Toll like receptors (TLRs). Activation of the adaptive immune system was evaluated by monitoring upregulation of surface receptors on dendritic cells (DCs) and CD4+ T cell proliferation in response to IV solution of Remicade®. Our results indicate that subvisible particles in Remicade®-saline solution have a significant role in activation of the immune system but there are extrinsic factors potentially contributed by the in-line filters or other process parameters that also contribute to immune system activation., (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Background: Early-stage and intermediate-stage nasopharyngeal cancer (NPC) generally carry a good prognosis, but for patients with recurrent, metastatic disease, options are limited. In the current study, the authors present a phase 1/2 study to evaluate the efficacy of Epstein-Barr virus (EBV)-stimulated cytotoxic T-lymphocyte (EBV-CTL) immunotherapy in this patient population., Methods: Screening for patients with active, recurrent, metastatic EBV-associated NPC began in February 2007, and the study was closed to accrual in January 2012. After informed consent was obtained, patients had their blood drawn to initiate manufacturing of the EBV-CTL product. During product manufacturing, patients were placed on interim standard-of-care chemotherapy, and only after disease progression on the interim chemotherapy did patients receive investigational immunotherapy. Patients were restaged every 2 months until disease progression and then followed for survival., Results: A total of 28 patients were enrolled, and 21 patients were treated. There was 1 complete response achieved, and at the time of last follow-up, the patient had been in remission for >8 years since treatment. The median progression-free survival was 2.2 months, and the median overall survival was 16.7 months. Two other patients, after failing EBV-CTL immunotherapy, unexpectedly demonstrated strong responses to the chemotherapy regimens they had previously failed. Patient EBV viral load and EBV-CTL specificity for tumor-associated viral antigens did not appear to correlate with clinical response., Conclusions: A durable response was observed with EBV-CTL immunotherapy, but the overall response rate for patients with recurrent, metastatic NPC was low. Further research is necessary to increase the efficacy of EBV-specific immunotherapy in patients with incurable NPC, and to characterize mechanisms for refacilitation to chemotherapy. Cancer 2017;123:2642-50. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

An In Vitro Comparative Immunogenicity Assessment (IVCIA) assay was evaluated as a tool for predicting the potential relative immunogenicity of biotherapeutic attributes. Peripheral blood mononuclear cells from up to 50 healthy naïve human donors were monitored up to 8 days for T-cell proliferation, the number of IL-2 or IFN-γ secreting cells, and the concentration of a panel of secreted cytokines. The response in the assay to 10 monoclonal antibodies was found to be in agreement with the clinical immunogenicity, suggesting that the assay might be applied to immunogenicity risk assessment of antibody biotherapeutic attributes. However, the response in the assay is a measure of T-cell functional activity and the alignment with clinical immunogenicity depends on several other factors. The assay was sensitive to sequence variants and could differentiate single point mutations of the same biotherapeutic. Nine mAbs that were highly aggregated by stirring induced a higher response in the assay than the original mAbs before stirring stress, in a manner that did not match the relative T-cell response of the original mAbs. In contrast, mAbs that were glycated by different sugars (galactose, glucose, and mannose) showed little to no increase in response in the assay above the response to the original mAbs before glycation treatment. The assay was also used successfully to assess similarity between multiple lots of the same mAb, both from the same manufacturer and from different manufacturers (biosimilars). A strategy for using the IVCIA assay for immunogenicity risk assessment during the entire lifespan development of biopharmaceuticals is proposed.