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An adaptable in vitro cytokine release assay (CRA): Susceptibility to cytokine storm in COVID-19 as a model

2024-12-17T03:35:08Z

Title: An adaptable in vitro cytokine release assay (CRA): Susceptibility to cytokine storm in COVID-19 as a model Authors: Alam, Masih; Choudhury, Rawshan; Lamers, Robert-Jan Abstract: Translational in vitro models such as cytokine release assay (CRA) are essential to assess the susceptibility to cytokine storm or CRS in a non-interventional manner in a human in vitro laboratory setting. Such models are also helpful to unravel disease mechanisms, to study the effects of new therapeutics and vaccines thereon and to diagnose or monitor diseases. Such assay will be important in predicting, planning and preparing for hospital intensive care units that are needed during the course of a pandemic. We present a CRA that can be adapted for assessing acute cytokine release risk against viral antigens, and potentially be used for cytokine storm simulation in viral infection outbreaks. We have used SARS-CoV-2 antigens and COVID-19 as a model. The assay can be challenged by changed or mutated forms of a virus in follow on waves of the epidemic and it can easily be modified for other future pandemics. We show that the membrane protein of SARS-CoV-2 is playing a major role in cytokine release (CR), mainly that of IL-6, IFNγ, TNFα and IL-8, that may be associated with COVID-19. These results are in agreement with recent clinical findings and new vaccine designs.

Mucosal delivery of RNA vaccines by Newcastle disease virus vectors

2024-12-17T03:32:33Z

Title: Mucosal delivery of RNA vaccines by Newcastle disease virus vectors Authors: García-Sastre, Adolfo Abstract: The rapid evolution of SARS-CoV-2 since its pandemic outbreak has underscored the need for improved SARS-CoV-2 vaccines that efficiently reduce not only hospitalizations and deaths, but also infections and transmission. This might be achieved by a new generation of intranasally administered SARS-CoV-2 vaccines to stimulate protective mucosal immunity. Among all different approaches, preclinical and clinical information using Newcastle Disease Virus (NDV)-vectors expressing S of SARS-CoV2 as a COVID-19 vaccine show the potential of this vaccine platform as an affordable, highly immunogenic, safe strategy to intranasally vaccinate humans against SARS-CoV-2 and other infectious diseases. These vaccine vectors consist on the use of a harmless avian negative strand RNA virus to deliver intranasally a self-replicating RNA expressing the vaccine antigen in the cells of the respiratory mucosa. The vector also incorporates the antigen in the virus particle used for RNA delivery, thus combining the properties of nanoparticle-based and RNA-based vaccines. Other advantages of NDV-based vectors include the worldwide availability of manufacturing facilities for their production and their stability at non-freezing temperatures. While phase 3 clinical studies to evaluate efficacy are still pending, phase 1 and 2 clinical studies have demonstrated the safety and immunogenicity of NDV-S vaccines against SARS-CoV-2.

Chemotherapy induces plasmatic antioxidant changes in pediatric patients with acute lymphoid leukemia B that correlate to disease prognosis

2024-12-17T03:31:47Z

Title: Chemotherapy induces plasmatic antioxidant changes in pediatric patients with acute lymphoid leukemia B that correlate to disease prognosis Authors: Ricardo Garbim, Matheus; Ellen Broto, Geise; Celso Trigo, Fausto Abstract: Pediatric acute lymphoid leukemias (ALL) is the most common childhood cancer, and cytotoxic chemotherapy remains the primary treatment option. Chemotherapic drugs act by oxidative stress generation, but their clinical meaning is poorly understood. During the chemotherapy schedule, this study evaluated the antioxidant profile of peripheral blood samples from 34 patients diagnosed with type B-cell ALL (B-ALL). Peripheral blood samples were collected at diagnosis (D0) and during the induction, consolidation, and maintenance phases. The plasma total antioxidant capacity (TRAP) was determined using the high-sensitivity chemiluminescence technique. Antioxidant levels were higher on D0 compared to day 7 after treatment starting (D7) in the induction phase (28.68–1194.71 μM Trolox, p = 0.0178) and in the high-risk group (age > ten years and/or with white blood cell counts and/or > 50,000 white blood cells/m3 at diagnosis) concerning low-risk patients (253.79–1194.71 μM Trolox, p = 0.0314). Reduced TRAP was also detected in patients who died compared to those who survived (392.42–1194.71 μM Trolox, p = 0.0278). Patients under consolidation (56.14–352.05 μM Trolox, p=<0.0001) and maintenance (30.48–672.99 μM Trolox, p=<0.0001) showed a significant reduction in TRAP levels compared to those from the induction phase (28.68–1390.26 μM Trolox), reaching levels similar to cured patients out of treatment (64.82–437.82 μM Trolox). These findings suggest that the variation of the total antioxidant capacity in B-ALL during chemotherapy is a parameter that correlates to some predictors of disease prognosis.

New insights into the tumour immune microenvironment of nasopharyngeal carcinoma

2024-12-17T03:24:39Z

Title: New insights into the tumour immune microenvironment of nasopharyngeal carcinoma Authors: Forder, Aisling; L. Stewart, Greg; Telkar, Nikita; L. Lam, Wan; Garnis, Cathie Abstract: Nasopharyngeal carcinoma (NPC) is unique among head and neck cancers for its strong causative association with Epstein Barr-Virus and high levels of immune infiltration that play a role in pathogenesis. As such, immunotherapy for the treatment of NPC is a promising area of research in the pursuit of improving patient outcomes. Understanding the tumour immune microenvironment (TIME) of NPC is the key to developing targeted immunotherapies and stratifying patients to determine optimal treatment regimens. Recent research has uncovered distinct characteristics of the TIME in NPC as well as important differences between the different disease subtypes; however, reviewing the state of the field reveals a further need for the application of novel techniques like multiplexed hyperspectral imaging and mass cytometry. These techniques can be used to identify spatial, compositional, and functional aspects of the TIME in NPC such as immune cell sociology, novel immune populations, and differences in immune-related signalling pathways in NPC in order to identify clinically relevant characteristics for targeted immunotherapy development and biomarker discovery