The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine

Viruses, Год журнала: 2023, Номер 15(1), С. 204 - 204

Опубликована: Янв. 11, 2023

The adenovirus vector platform remains one of the most efficient toolboxes for generation transfer vehicles used in gene therapy and virotherapy to treat tumors, as well vaccines protect from infectious diseases. genome capsids can be modified using highly techniques, vectors produced at high titers, which facilitates their rapid adaptation current needs disease applications. Over recent years, has been center attention vaccine development against ongoing coronavirus SARS-CoV-2/COVID-19 pandemic. worldwide deployment these greatly deepened knowledge on virus-host interactions highlighted need further improve effectiveness safety not only adenovirus-based but also oncolytic vectors. Based evidence, we discuss here how adenoviral improved by intelligent molecular design. This review covers full spectrum state-of-the-art strategies avoid vector-induced side effects ranging vectorization non-canonical types novel engineering techniques.

Язык: Английский

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Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial

Nature Medicine, Год журнала: 2024, Номер 30(9), С. 2631 - 2640

Опубликована: Июнь 20, 2024

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity UB-312, an active immunotherapeutic targeting pathological αSyn, PD. The primary outcome measures were adverse event frequency change anti-αSyn antibody titers blood cerebrospinal fluid (CSF). Exploratory outcomes changes clinical scales biomarker-based engagement as measured by seed amplification assays. Twenty randomized 7:3 (UB-312:placebo) into 300/100/100 μg 300/300/300 (weeks 1, 5 13) intramuscular prime-boost dose groups. Safety was similar across groups; events mostly mild transient. Two experienced three serious total, one possibly treatment related; all resolved without sequalae. Anti-αSyn antibodies serum from 12/13 CSF 5/13 who received UB-312 doses confirmed immunogenicity. Mean (in log-dilution factor) increased baseline 1.398 1.354, peaked at week 29 2.520 2.133, for μg, respectively. 0 0.182 0.032 21, analyses showed no statistical differences but a significant reduction αSyn seeds subset UB-312-treated patients. These data support further development. ClinicalTrials.gov: NCT04075318 .

Язык: Английский

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Incidence and management of the main serious adverse events reported after COVID‐19 vaccination

Pharmacology Research & Perspectives, Год журнала: 2024, Номер 12(3)

Опубликована: Июнь 1, 2024

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China 2019. Soon after, it was declared a pandemic World Health Organization. The health crisis imposed new virus and its rapid spread worldwide prompted fast development of vaccines. For time human history, two vaccines based on recombinant genetic material technology were approved for use. These mRNA applied massive immunization programs around world, followed other more traditional approaches. Even though all tested clinical trials prior to their general administration, serious adverse events, usually very low incidence, mostly identified after application millions doses. Establishing direct correlation (the cause-effect paradigm) between vaccination appearance effects has proven challenging. This review focuses main observed vaccination, including anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, transverse myelitis reported context COVID-19 vaccination. We highlight symptoms, laboratory tests required an adequate diagnosis, briefly outline recommended treatments these effects. aim this work is increase awareness among healthcare personnel about events that may arise post-vaccination. Regardless ongoing discussion safety must be promptly treated effectively reduce risk complications.

Язык: Английский

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New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 28, 2023

Platelet factor 4 (PF4), also known as chemokine (C-X-C motif) ligand (CXCL4), is a specific protein synthesized from platelet α particles. The combination of PF4 and heparin to form antigenic complexes an important mechanism in the pathogenesis heparin-induced thrombocytopenia (HIT), but vaccine-induced immune thrombotic (VITT) related COVID-19 vaccine makes research hotspot again. Similar HIT, vaccines, bacteria, other non-heparin exposure, can interact with negatively charged polyanions participate thrombosis. These anions include cell surface mucopolysaccharides, polyphosphates, DNA endothelial cells, or von Willebrand (VWF). Among them, PF4–VWF, new complex, may induce promote formation immune-associated thrombosis expected become target therapeutic direction. For both HIT VITT, there no effective targeted treatment except discontinuation suspected drugs. development drugs based on action have unmet clinical need. Here, this study systematically reviewed characteristics pathophysiological mechanisms VWF, elaborated potential PF4–VWF complex thrombosis, summarized current status drug for discussed possibility biomarker early events. Moreover, key points basic evaluation are put forward study.

Язык: Английский

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Immunothrombotic involvement in COVID-19

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 335 - 352

Опубликована: Янв. 1, 2025

Язык: Английский

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Thromboembolic Events in the Era of COVID‐19: A Detailed Narrative Review

Canadian Journal of Infectious Diseases and Medical Microbiology, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

COVID-19, caused by the SARS-CoV-2 virus, is not only characterized respiratory symptoms but also associated with a wide range of systemic complications, including significant hematologic abnormalities. This comprehensive review current literature, using PubMed and Google Scholar, on pathophysiology incidence thromboembolic events in COVID-19 patients thromboprophylaxis. infection induces prothrombotic state through dysregulation renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction, elevated von Willebrand factor (vWF), dysregulated immune response involving complement neutrophil extracellular traps (NETs). As result, complications have emerged cases, occurring more frequently severe cases hospitalized patients. These thrombotic affect both venous arterial circulation, increased incidences deep thrombosis (DVT), pulmonary embolism (PE), thrombosis, myocardial infarction (MI). While DVT PE are common, literature highlights potential lethal consequences thromboembolism (ATE). briefly examines ongoing discussions regarding use anticoagulants for prevention theoretically promising, studies yielded varied outcomes: Some suggest benefits, whereas others report an risk bleeding among Therefore, further large-scale needed to assess efficacy safety thromboprophylaxis

Язык: Английский

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Cardiovascular Sequelae of the COVID-19 Vaccines

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Vaccines against COVID-19 present a key tool in lowering the morbidity, mortality, and transmission of disease, but they also strongly controversial topic. As result, adverse effects vaccine have been under scrutiny by public eye. A comprehensive summary cardiovascular (CV) vaccines is vital for clinical recognition rare events, determining health implications, creating base future research. In May 2023, search was conducted PubMed Cochrane databases to identify literature on CV complications resulting from vaccine. All articles with relevant data discussion regarding were included review. total, 4419 screened, 166 The vaccine-associated events encompassed following conditions: myocarditis, pericarditis, acute coronary syndrome, stress cardiomyopathy, hypertension, isolated tachycardia, myocardial infarction (MI) nonobstructive arteries (MINOCA), cardiac arrest, vaccine-induced thrombotic thrombocytopenia (VITT), MI, cerebral venous thrombosis (CVT), deep vein (DVT), pulmonary embolism (PE), other disorders. Among these, myocarditis thrombosis, especially VITT, emerged as most frequently cited reviewed literature. Ranges incidences recorded among articles: myocarditis: 2 17 per million, VITT: 3-10 CVST: 2.6-10 MI: 3-4 million. entail potential although at low incidence, some which exhibit notable severity. These demographic specificity vaccine-specific profiles. are uniformly nature. existing body evidence offers limited support assertion that may elevate baseline risk long term. However, available research greater than six months scarce.

Язык: Английский

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Acute extensive pulmonary embolism after mRNA SARS-CoV-2 immunization

Radiology Case Reports, Год журнала: 2024, Номер 19(9), С. 4087 - 4090

Опубликована: Июль 13, 2024

COVID-19 vaccines, a cornerstone of the fight against disease have generally proven to be safe with most commonly reported side effects being mild and self-limiting. Uncommon severe adverse like thromboembolism been during postmarketing surveillance. Viral-based vector vaccines implicated in these reports. Our report however portrays case 26-year-old female who developed extensive pulmonary embolism following administration Pfizer- BNT162b2 mRNA vaccine. The patient did not any risk factors for thromboembolism. She was admitted, put on enoxaparin, given Altaplase thrombolytic therapy. Her condition improved she discharged Apixaban. Thrombophilia screen performed 6-month follow-up negative resolution thrombosis, Apixaban stopped. highlights importance continued surveillance uncommon need prompt diagnosis management such effects.

Язык: Английский

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A review of the scientific literature on experimental toxicity studies of COVID-19 vaccines, with special attention to publications in toxicology journals

Archives of Toxicology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 3, 2024

Abstract Since the reports of first cases COVID-19, in less than 5 years, a huge number documents regarding that disease and coronavirus (SARS-CoV-2), responsible for infection, have been published. The tremendous scientific covers many topics on different issues directly related to COVID-19/SARS-CoV-2. articles—including reviews—reporting adverse/side effects approved COVID-19 vaccines is considerable. A wide range reported humans after vaccination: thrombotic events/thrombocytopenia, myocarditis/pericarditis, cutaneous reactions, immune-mediated effects, psychiatric adverse events, systemic lupus erythematosus, reproductive toxicity, other miscellaneous effects. In contrast, information nonclinical studies conducted assess potential toxicity/adverse laboratory animals, comparatively very scarce. present review was aimed at revising literature animals toxic/adverse vaccines. addition, investigations those specific toxicology journals with highest impact factors examined one by one. results indicate most nonclinical/experimental adverse/toxic and/or candidates showed—in general terms—a good safety profile. Only some animal were certain found. However, rather surprising result has limited available (in databases PubMed Scopus) performed companies largest manufacturers mRNA world. It assumed these conducted. they not published journals, which does allow judgment international community, including toxicologists.

Язык: Английский

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Synergistic effect of SARS-CoV-2 infection and COVID-19 vaccination on the risk of venous thromboembolism

The American Journal of Medicine, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

Язык: Английский

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