scholarly journals Rapid Generation of Coronaviral Immunity Using Recombinant Peptide Modified Nanodiamonds

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 861
Author(s):  
Rostyslav Bilyy ◽  
Quentin Pagneux ◽  
Nathan François ◽  
Galyna Bila ◽  
Roman Grytsko ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutrophil Extracellular Traps ◽  
Fusion Inhibitor ◽  
Recombinant Peptide ◽  
Vaccine Candidates ◽  
Extracellular Traps ◽  
Vaccine Initiation ◽  
Rapid Generation ◽  
Living Organisms ◽  
High Level

Vaccination remains one of the most effective tools to prevent infectious diseases. To ensure that the best possible antigenic components are chosen to stimulate a cognitive immune response, boosting antigen presentation using adjuvants is common practice. Nanodiamond-based adjuvants are proposed here as a rapid and versatile platform for antigen conjugation, utilizing peptides common to different pathogenic strains and making this strategy a good candidate for a “ready-to-use” vaccine. Initiation of an inflammatory reaction with a resulting immune response is based on the ability of living organisms to entrap nanostructures such as nanodiamonds with neutrophil extracellular traps (NETs) formation. In this work, coronavirus peptide homological for MERS-CoV, fusion inhibitor, was conjugated to nanodiamonds and used to induce neutrophilic-driven self-limiting inflammation. The resulting adjuvant was safe and did not induce any tissue damage at the site of injection. Mice immunization resulted in IgG titers of ¼,000 within 28 days. Immunization of rabbits resulted in the formation of a high level of antibodies persistently present for up to 120 days after the first immunization (animal lifespan ~3 years). The peptide used for immunization proved to be reactive with sera of convalescent COVID patients, demonstrating the possibility of developing pancoronaviral vaccine candidates.

scholarly journals Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19

2020 ◽  
Author(s):  
Corleone Delaveris ◽  
Aaron Wilk ◽  
Nicholas Riley ◽  
Jessica Stark ◽  
Samuel Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Strategy ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Activation ◽  
Signaling Cascade ◽  
Peripheral Inflammation ◽  
Pulmonary Tissue ◽  
Extracellular Traps ◽  
Cell Death Pathway ◽  
Key Factor

Severe cases of coronavirus disease 2019 (COVID-19), caused by infection with SARS-Cov-2, are characterized by a hyperinflammatory immune response that leads to numerous complications. Production of proinflammatory neutrophil extracellular traps (NETs) has been suggested to be a key factor in inducing a hyperinflammatory signaling cascade, allegedly causing both pulmonary tissue damage and peripheral inflammation. Accordingly, therapeutic blockage of neutrophil activation and NETosis, the cell death pathway accompanying NET formation, could limit respiratory damage and death from severe COVID-19. Here, we demonstrate that synthetic glycopolymers that activate the neutrophil checkpoint receptor Siglec-9 suppress NETosis induced by agonists of viral toll-like receptors (TLRs) and plasma from patients with severe COVID-19. Thus, Siglec-9 agonism is a promising therapeutic strategy to curb neutrophilic hyperinflammation in COVID-19.<br>

scholarly journals DEspRhigh neutrophils are associated with critical illness in COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joanne T. deKay ◽  
Ivette F. Emery ◽  
Jonathan Rud ◽  
Ashley Eldridge ◽  
Christine Lord ◽  
...  
Keyword(s):  
Immune Cell ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Cytokines And Chemokines ◽  
Blood Smears ◽  
Secondary Tissue ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations ◽  
High Level ◽  
Negative Controls

AbstractSARS-CoV-2 infection results in a spectrum of outcomes from no symptoms to widely varying degrees of illness to death. A better understanding of the immune response to SARS-CoV-2 infection and subsequent, often excessive, inflammation may inform treatment decisions and reveal opportunities for therapy. We studied immune cell subpopulations and their associations with clinical parameters in a cohort of 26 patients with COVID-19. Following informed consent, we collected blood samples from hospitalized patients with COVID-19 within 72 h of admission. Flow cytometry was used to analyze white blood cell subpopulations. Plasma levels of cytokines and chemokines were measured using ELISA. Neutrophils undergoing neutrophil extracellular traps (NET) formation were evaluated in blood smears. We examined the immunophenotype of patients with COVID-19 in comparison to that of SARS-CoV-2 negative controls. A novel subset of pro-inflammatory neutrophils expressing a high level of dual endothelin-1 and VEGF signal peptide-activated receptor (DEspR) at the cell surface was found to be associated with elevated circulating CCL23, increased NETosis, and critical-severity COVID-19 illness. The potential to target this subpopulation of neutrophils to reduce secondary tissue damage caused by SARS-CoV-2 infection warrants further investigation.

scholarly journals Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-25 ◽  
Author(s):  
Sebastiano Cicco ◽  
Gerolamo Cicco ◽  
Vito Racanelli ◽  
Angelo Vacca
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Targeted Therapy ◽  
High Mobility ◽  
Neutrophil Extracellular Traps ◽  
Lung Cells ◽  
Extracellular Traps ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Excessive Inflammatory Response

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.

scholarly journals Penton-dodecahedron of fowl adenovirus serotype 4 as a vaccine candidate for the control of related diseases

2018 ◽  
Author(s):  
Qiuxia Tang ◽  
Ruyi Dangi ◽  
Li Qiu ◽  
Zengqi Yang ◽  
Xinglong Wang
Keyword(s):  
Immune Response ◽  
Recombinant Proteins ◽  
Vaccine Antigen ◽  
Penton Base ◽  
Adenovirus Serotype ◽  
Vaccine Candidates ◽  
Fowl Adenovirus ◽  
Infected Cells ◽  
High Level ◽  
Fowl Adenovirus Serotype 4

AbstractIn some serotypes of adenovirus (Ad), the penton base protein and attached trimeric fiber assemble into dodecameric virus-like particles called penton-dodecahedron (Pt-Dd), which can internalize into cells and can be used to deliver the vaccine antigen and drugs. Fowl adenovirus serotype 4 (FAdV-4) is an important poultry pathogens and causing seriously economic lost to poultry industry in China and several other counties. The produce of Pt-Dd in FAdV-4 infected cells as well as in those infected with the recombinant human Ad expressing fiber-1, fiber-2, and penton base was determine by Transmission electron microscopy (TEM). For the First time, we proved that FAdV-4 produced Pt-Dd in infected cells, which can also be assembled by the overexpressed recombinant proteins fiber-1, fiber-2, and penton base. Pt-Dd, as well as the recombinant proteins fiber-1, fiber-2, and penton base, were then used to immunize chickens. The humoral immune response, cell mediate immune response (CMI), and challenge results were used to evaluate the immune efficacy of the vaccine candidates. Pt-Dd induced the highest level of enzyme-linked immunosorbent assay antibodies and high levels of CMI, showing a significantly (p < 0.05) high level of interferon γ, interleukin-4, and major histocompatibility complex II expressions in peripheral blood mononuclear cells at 48 h post-infection. The challenge results showed that Pt-Dd, inactivated FAdV-4 vaccine, as well as fiber-1 induced the best protection (100%), followed by fiber-2 (80%) and penton (67%). The present study showed that FAdV-4-Pt-Dd and recombinant fiber-1 are good FAdV-4 vaccine candidates and could be used to replace the tissue-sourced inactivated FAdV-4 vaccine.ImportanceFAdV-4-Pt-Dds were discovered in FAdV-4 infected cells, and which were also assembled in cells transduced with recombinant human adenovirus expressing fiber-1, fiber-2, and penton base. FAdV-4-Pt-Dds internalize into cells with high efficiency, so that it can be used for delivery vaccine antigen or drugs. Immunization chickens with Pt-Dd and fiber-1 obtained by transduction HEK-293T cells induced significant high level humoral and cellular mediated immune responses, and also 100% challenge protection in chickens indicating that they are good FAdV-4 vaccine candidates. What more, the Pt-Dd obtained by transduction HEK-293T cell would have no DNA and adenovirus contamination as adenovirus could not package in HEK-293T cells.

scholarly journals High Level of Neutrophil Extracellular Traps Correlates With Poor Prognosis of Severe Influenza A Infection

2018 ◽  
Vol 217 (3) ◽  
pp. 428-437 ◽  
Author(s):  
Liuluan Zhu ◽  
Lu Liu ◽  
Yue Zhang ◽  
Lin Pu ◽  
Jingyuan Liu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Influenza A ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Severe Influenza ◽  
High Level

scholarly journals The Dual Role of Myeloperoxidase in Immune Response

2020 ◽  
Vol 21 (21) ◽  
pp. 8057 ◽  
Author(s):  
Jürgen Arnhold
Keyword(s):  
Immune Response ◽  
Innate Immune System ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Major Constituent ◽  
Extracellular Traps ◽  
Atherosclerotic Lesions ◽  
Disease Specific ◽  
Frustrated Phagocytosis

The heme protein myeloperoxidase (MPO) is a major constituent of neutrophils. As a key mediator of the innate immune system, neutrophils are rapidly recruited to inflammatory sites, where they recognize, phagocytose, and inactivate foreign microorganisms. In the newly formed phagosomes, MPO is involved in the creation and maintenance of an alkaline milieu, which is optimal in combatting microbes. Myeloperoxidase is also a key component in neutrophil extracellular traps. These helpful properties are contrasted by the release of MPO and other neutrophil constituents from necrotic cells or as a result of frustrated phagocytosis. Although MPO is inactivated by the plasma protein ceruloplasmin, it can interact with negatively charged components of serum and the extracellular matrix. In cardiovascular diseases and many other disease scenarios, active MPO and MPO-modified targets are present in atherosclerotic lesions and other disease-specific locations. This implies an involvement of neutrophils, MPO, and other neutrophil products in pathogenesis mechanisms. This review critically reflects on the beneficial and harmful functions of MPO against the background of immune response.

scholarly journals ROLE OF NEUTROPHIL EXTRACELLULAR TRAPS IN ESPECIALLY DANGEROUS BACTERIAL INFECTIONS

2016 ◽  
pp. 95-104
Author(s):  
A. L. Kravtsov
Keyword(s):  
Experimental Data ◽  
Immune Response ◽  
Bacterial Infections ◽  
Neutrophil Extracellular Traps ◽  
Bactericidal Effect ◽  
Pathogenic Microorganisms ◽  
Extracellular Traps ◽  
Contemporary View ◽  
Causative Agents

Novel data on neutrophil extracellular traps (NET), carrying out capture and killing of pathogenic microorganisms with higher effectiveness than during phagocytosis, are presented. A contemporary view on how neutrophils choose intracellular (phagocytosis) or extracellular (NETosis) mechanism of bactericidity during interaction with pathogenic microorganisms is given. Experimental data on the presence in causative agents of plague, cholera and melioidosis of mechanisms of protection from bactericidal effect of NET, as well as NET’S role in regulation of immune response and sepsis development are analyzed.

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