Progress in molecular biology and translational science, Год журнала: 2023, Номер unknown
Опубликована: Янв. 1, 2023
Язык: Английский
Trends in Molecular Medicine, Год журнала: 2022, Номер 28(7), С. 542 - 554
Опубликована: Апрель 21, 2022
Язык: Английский
Процитировано
199
Biomedicines, Год журнала: 2023, Номер 11(8), С. 2287 - 2287
Опубликована: Авг. 17, 2023
The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. production of ‘safe effective’ vaccines was a key public health target. Sadly, unprecedented high rates adverse events have overshadowed the benefits. This two-part narrative review presents evidence for widespread harms novel product mRNA adenovectorDNA is in attempting provide thorough overview arising from new technology that relied on human cells producing foreign antigen has pathogenicity. first paper explores peer-reviewed data counter attached these technologies. Spike protein pathogenicity, termed ‘spikeopathy’, whether SARS-CoV-2 virus or produced by vaccine gene codes, akin ‘synthetic virus’, increasingly understood terms molecular biology pathophysiology. Pharmacokinetic transfection through body tissues distant injection site lipid-nanoparticles viral-vector carriers means ‘spikeopathy’ can affect organs. inflammatory properties nanoparticles used ferry mRNA; N1-methylpseudouridine employed prolong synthetic function; biodistribution DNA codes translated spike proteins, autoimmunity via contribute harmful effects. reviews autoimmune, cardiovascular, neurological, potential oncological effects, autopsy spikeopathy. With gene-based therapeutic technologies planned, re-evaluation necessary timely.
Язык: Английский
Процитировано
51
Vaccines, Год журнала: 2024, Номер 12(4), С. 409 - 409
Опубликована: Апрель 12, 2024
Chitosan, a natural polysaccharide derived from chitin, possesses biocompatibility, biodegradability, and mucoadhesive characteristics, making it an attractive material for the delivery of mRNA payloads to nasal mucosa promoting their uptake by target cells such as epithelial immune (e.g., dendritic macrophages). In this project, we aimed at developing novel lipid-based nanoformulations counteract pandemic caused SARS-CoV-2 virus. The formulations achieved encapsulation efficiency ~80.2% with chitosan-lipid nanoparticles, measured RiboGreen assay. Furthermore, evaluation Spike (S) receptor-binding domain (RBD) expression via ELISA our vaccine showed transfection levels in human embryonic kidney (HEK 293), lung carcinoma (A549), (DC 2.4) equal 9.9 ± 0.1 ng/mL (174.7 1.1 fold change untreated (UT)), 7.0 0.2 (128.1 4.9 UT), 0.9 0.0 (18.0 respectively. Our most promising formulation was also demonstrated be amenable lyophilization minimal degradation loaded mRNA, paving way towards more accessible stable vaccine. Preliminary vivo studies mice were performed assess systemic local responses. Nasal bronchoalveolar lavage fluid (BALF) wash that utilizing optimized resulted antibody concentrations did not trigger any response. However, if further improved developed, could potentially contribute management COVID-19 through nasopharyngeal immunization strategies.
Язык: Английский
Процитировано
7
Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)
Опубликована: Окт. 10, 2023
Abstract Inflammation, although necessary to fight infections, becomes a threat when it exceeds the capability of immune system control it. In addition, inflammation is cause and/or symptom many different disorders, including metabolic, neurodegenerative, autoimmune and cardiovascular diseases. Comorbidities advanced age are typical predictors more severe cases seasonal viral infection, with COVID-19 clear example. The primary importance mitogen-activated protein kinases (MAPKs) in course evident mechanisms by which cells infected SARS-CoV-2; cytokine storm that profoundly worsens patient’s condition; pathogenesis diseases, such as diabetes, obesity, hypertension, contribute worsened prognosis; post-COVID-19 complications, brain fog thrombosis. An increasing number reports have revealed MAPKs regulated carbon dioxide (CO 2 ); hence, we reviewed literature identify associations between CO possible therapeutic benefits resulting from elevation levels. regulates key processes leading inflammation, effects (or bicarbonate, HCO 3 − ) been documented all abovementioned comorbidities complications play roles. overlapping MAPK signalling pathways contexts allergy, apoptosis cell survival, pulmonary oedema (alveolar fluid resorption), mechanical ventilation–induced responses lungs related mitochondria also discussed.
Язык: Английский
Процитировано
15
Journal of Medical Virology, Год журнала: 2022, Номер 94(9), С. 4071 - 4087
Опубликована: Апрель 30, 2022
Since the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection, global public health and economy have suffered unprecedented damage. Based on increasing related literature, characteristics pathogenic mechanisms virus, epidemiological clinical features are being rapidly discovered. The spike glycoprotein (S protein), as a key antigen SARS-CoV-2 for developing vaccines, antibodies, drug targets, has been shown to play an important role in viral entry, tissue tropism, pathogenesis. In this review, we summarize molecular interaction between S protein host factors, especially receptor-mediated modulation signaling pathways, highlight progression potential therapeutic prophylactic agents prevention treatment infection.
Язык: Английский
Процитировано
14
Vaccine X, Год журнала: 2024, Номер 16, С. 100443 - 100443
Опубликована: Янв. 1, 2024
The severe acute respiratory syndrome coronavirus 2 -related global COVID-19 pandemic has been impacting millions of people since its outbreak in 2020. vaccination proven highly efficient reducing illness severity and preventing infection-related fatalities. World Health Organization granted emergency use approval to multiple, including protein subunit technology-based, vaccines. Foreseeably, additional vaccine development would be essential meet the accessible growing demand for effective vaccines, especially Low-Middle-Income Countries (LMIC). SARS-CoV-2 spike receptor binding domain (RBD), as primary target neutralizing antibodies, holds significant potential future development. In this study, we developed a recombinant Escherichia coli-expressed RBD (rRBD) candidate evaluated immunogenicity preliminary toxicity BALB/c mice. rRBD induced humoral immune response from day 7 post-vaccination and, following booster doses, IgG levels increased dramatically Interestingly, our also significantly cellular response, indicated by incrased IFN-ɣ-producing cell numbers. We observed no adverse effect or local reactogenicity either control treated Taken together, discoveries could potentially support cost-effective antigen production, which LMICs particularly benefit.
Язык: Английский
Процитировано
2
Scientific Reports, Год журнала: 2022, Номер 12(1)
Опубликована: Окт. 12, 2022
Abstract The emergence of Omicron variant raises great concerns because its rapid transmissibility and numerous mutations in spike protein (S-protein). S-protein can act as a pathogen-associated molecular pattern complement activator well antigen. We compared some immune characteristics trimer S-proteins for wild type (WT-S) B.1.1.529 (Omicron-S) to investigate whether the have affected pathogenicity antigenic shift. results indicated that WT-S Omicron-S directly activated nuclear factor-κB (NF-κB) induced release pro-inflammatory cytokines macrophages, but actions were weaker. These inflammatory reactions could be abrogated by Toll-like receptor 4 antagonist TAK-242. Two failed induce production antiviral interferon-β. In contrast effects, ability two activate was comparable. also binding high-titer anti-WT-receptor-binding domain antibody. data showed strongly bound this antibody, while completely off-target. Collectively, impact on epitopes S-protein, little effect complement. Addressing these issues helpful more adequate understanding vaccine breakthrough infection.
Язык: Английский
Процитировано
11
Archives of Virology, Год журнала: 2023, Номер 168(7)
Опубликована: Июнь 13, 2023
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection is associated with a high mortality rate. clinical course attributed to the severity of pneumonia and systemic complications. In COVID-19 patients murine models SARS-CoV-2 infection, may be accompanied excessive production cytokines, leading an accumulation immune cells in affected organs such as lungs. Previous reports have shown that antagonizes interferon (IFN)-dependent antiviral response, thereby preventing expression IFN-stimulated genes (ISGs). Lower IFN levels been linked more-severe COVID-19. Interleukin 27 (IL27) heterodimeric cytokine composed IL27p28 EBI3 subunits, which induce both pro- anti-inflammatory responses. Recently, we others reported IL27 also induces strong response IFN-independent manner. Here, investigated transcription subunits patients. results show modulates TLR1/2-MyD88 signaling PBMCs monocytes NF-κB activation NF-κB-target are dependent on robust pro-inflammatory including EBI3; activates IRF1 mRNA expression. suggest STAT1-dependent manner COVID-derived function Similar were observed macrophages stimulated spike protein. Thus, can trigger host, suggesting possibility novel therapeutics against humans.
Язык: Английский
Процитировано
6
Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 12
Опубликована: Март 6, 2024
Prolyl-4-hydroxylases (
Язык: Английский
Процитировано
2
Pharmaceutics, Год журнала: 2023, Номер 15(3), С. 825 - 825
Опубликована: Март 2, 2023
Dendritic cells (DCs) are the most specialized and proficient antigen-presenting cells. They bridge innate adaptive immunity display a powerful capacity to prime antigen-specific T The interaction of DCs with receptor-binding domain spike (S) protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pivotal step induce effective against S protein-based vaccination protocols, as well SARS-CoV-2 virus. Herein, we describe cellular molecular events triggered by virus-like particles (VLPs) containing motif in human monocyte-derived dendritic cells, or, controls, presence Toll-like receptors (TLR)3 TLR7/8 agonists, comprehending cell maturation their crosstalk results demonstrated that VLPs boosted expression major histocompatibility complex molecules co-stimulatory DCs, indicating maturation. Furthermore, DCs’ promoted activation NF-kB pathway, very important intracellular signalling pathway responsible for triggering secretion proinflammatory cytokines. Additionally, co-culture CD4+ (mainly CD4+Tbet+) CD8+ proliferation. Our suggested increase immunity, involving DC polarization towards type 1 profile. By providing deeper insight into mechanisms regulation immune system these findings will enable design vaccines SARS-CoV-2.
Язык: Английский
Процитировано
5