Enhanced SARS-CoV-2 breakthrough infections in patients with hematologic and solid cancers due to Omicron

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(5), P. 444 - 446

Published: April 12, 2022

Language: Английский

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Treatment of COVID‐19 patients with a SARS‐CoV‐2‐specific siRNA‐peptide dendrimer formulation

Allergy, Journal Year: 2023, Volume and Issue: 78(6), P. 1639 - 1653

Published: Feb. 1, 2023

Severe acute respiratory syndrome corona virus (SARS-CoV-2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety efficacy of a SARS-CoV-2-specific siRNA-peptide dendrimer formulation MIR 19® (siR-7-EM/KK-46) targeting conserved sequence in known SARS-CoV-2 variants for treatment COVID-19.We conducted an open-label, randomized, controlled multicenter phase II trial (NCT05184127) evaluating inhaled siR-7-EM/KK-46 (3.7 mg 11.1 mg/day: low high dose, respectively) comparison with standard etiotropic drug (control group) patients hospitalized moderate COVID-19 (N = 52 each group). The primary endpoint was the time clinical improvement according predefined criteria within 14 days randomization.Patients from low-dose group achieved defined by simultaneous achievement relief fever, normalization rate, reduction coughing, oxygen saturation >95% 48 h significantly earlier (median 6 days; 95% confidence interval [CI]: 5-7, HR 1.75, p .0005) than control (8 CI: 7-10). No significant observed high-dose group. Adverse events were reported 26 (50.00%), 25 (48.08%), 28 (53.85%) low-, group, respectively. None them associated siR-7-EM/KK-46.siR-7-EM/KK-46, is safe, well tolerated reduces compared therapy randomized trial.

Language: Английский

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Importance, Applications and Features of Assays Measuring SARS-CoV-2 Neutralizing Antibodies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5352 - 5352

Published: March 10, 2023

More than three years ago, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused unforeseen COVID-19 pandemic with millions of deaths. In meantime, SARS-CoV-2 has become endemic and is now part repertoire viruses causing seasonal severe respiratory infections. Due to several factors, among them development immunity through natural infection, vaccination current dominance seemingly less pathogenic strains belonging omicron lineage, situation stabilized. However, challenges remain possible new occurrence highly variants remains a threat. Here we review development, features importance assays measuring neutralizing antibodies (NAbs). particular focus on in vitro infection molecular interaction studying binding receptor domain (RBD) its cognate cellular ACE2. These assays, but not measurement SARS-CoV-2-specific per se, can inform us whether produced by convalescent or vaccinated subjects may protect against thus have potential predict risk becoming newly infected. This information extremely important given fact that considerable number subjects, vulnerable persons, respond poorly production antibodies. Furthermore, these allow determine evaluate virus-neutralizing capacity induced vaccines administration plasma-, immunoglobulin preparations, monoclonal antibodies, ACE2 synthetic compounds be used for therapy assist preclinical evaluation vaccines. Both types relatively quickly adapted emerging virus about magnitude cross-neutralization, which even estimate infected appearing variants. Given paramount discuss their specific features, advantages disadvantages, technical aspects yet fully resolved issues, such as cut-off levels predicting degree vivo protection.

Language: Английский

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Vaccine based on folded receptor binding domain‐PreS fusion protein with potential to induce sterilizing immunity to SARS‐CoV‐2 variants

Allergy, Journal Year: 2022, Volume and Issue: 77(8), P. 2431 - 2445

Published: March 31, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global COVID-19 pandemic. One possibility to control pandemic induce sterilizing immunity through induction and maintenance of neutralizing antibodies preventing SARS-CoV-2 from entering human cells replicate in.

Language: Английский

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Lower magnitude and faster waning of antibody responses to SARS-CoV-2 vaccination in anti-TNF-α-treated IBD patients are linked to lack of activation and expansion of cTfh1 cells and impaired B memory cell formation

EBioMedicine, Journal Year: 2023, Volume and Issue: 96, P. 104788 - 104788

Published: Sept. 4, 2023

Patients with inflammatory bowel disease (IBD) and healthy controls received primary SARS-CoV-2-mRNA vaccination a booster after six months. Anti-TNF-α-treated patients showed significantly lower antibody (Ab) levels faster waning than α4β7-integrin-antagonist recipients controls. This prospective cohort study aimed to elucidate the underlying mechanisms on basis of circulating T-follicular helper cells (cTfh) B memory cells.We measured SARS-CoV-2- Wuhan Omicron specific Abs, B- T-cell subsets at baseline kinetics Spike (S)-specific along distributions activated cTfh before vaccination.Lower Ab in anti-TNF-α treated IBD was associated low numbers total naïve vs. expanded plasmablasts prior vaccination. Along their against VOCs, reduced S-specific were identified 2nd dose which declined non-detectable 6 In contrast, α4β7-integrin-antagonists mounted retained high dose, pronounced increase that maintained or up Booster led strong Abs neutralizing capacity these groups, not case patients. Of note, particular post-booster correlated activation cTfh1 vaccination.The magnitude, persistence neutralization SARS-CoV-2 anti-TNF-α-treated impaired formation maintenance cells, likely due absent leading extra-follicular immune responses diminished cell diversification. These observations have implications for patient-tailored schedules/vaccines patients, irrespective disease.The funded by third party funding Institute Specific Prophylaxis Tropical Medicine Medical University Vienna. The funders had no role design, data collection, analyses, interpretation, writing report.

Language: Английский

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Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell®

Vaccines, Journal Year: 2023, Volume and Issue: 11(4), P. 874 - 874

Published: April 20, 2023

The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, S shows considerable sequence variations among variants concern. aim this study was to develop characterize a vaccine targeting highly conserved nucleocapsid (N) protein. Recombinant N expressed in Escherichia coli, purified homogeneity by chromatography characterized SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering differential scanning calorimetry. vaccine, formulated as squalane-based emulsion, used immunize Balb/c mice NOD SCID gamma (NSG) engrafted with human PBMCs, rabbits marmoset monkeys. Safety immunogenicity assessed via ELISA, cytokine titer assays CFSE dilution assays. protective effect studied SARS-CoV-2-infected Syrian hamsters. Immunization induced sustainable N-specific IgG responses an mixed Th1/Th2 response. In monkeys, CD4+/CD8+ T cell response observed. Vaccinated hamsters showed reduced lung histopathology, lower virus proliferation, weight relative body, faster body recovery. Convacell® thus is shown be effective may augment existing armamentarium against COVID-19.

Language: Английский

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Breakthrough Infections in SARS-CoV-2-Vaccinated Multiple Myeloma Patients Improve Cross-Protection against Omicron Variants

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 518 - 518

Published: May 9, 2024

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations breakthrough infections (BTIs) on antibody (Ab) levels cross-protection variants concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral cellular vaccine in MM patients stratified according disease stage/treatment into (1) monoclonal gammopathy undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) SCT IT, (4) progressed MM, healthy subjects (prospective cohort study). In contrast hu-1-specific Ab levels, Omicron-specific Abs their cross-neutralisation capacity remained low even three doses majority patients. particular, receiving anti-CD38 mAb those IT were responders showed delayed formation spike-specific B memory cells. However, hybrid immunity (i.e., vaccination infection) had improved against VOCs, yet the absence severe disease. Our results indicate that require frequent variant-adapted and/or changes other formulations/platforms, which might have similar immunological as BTIs.

Language: Английский

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Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 28, 2025

In this article we discuss characteristics of fusion protein-based SARS-CoV-2 vaccines. We focus on recombinant vaccine antigens comprising proteins consisting combinations SARS-CoV-2-derived or peptides antigens/peptides with SARS-CoV-2-unrelated proteins/peptides. These are made to increase the immunogenicity and/or enable special targeting immune system. The approach is exemplified solely in a proof concept study by using W-PreS-O, chimeric based single protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron BA.1 hepatitis B virus (HBV)-derived PreS surface antigen adsorbed aluminum hydroxide. W-PreS-O was evaluated Syrian hamsters which were immunized three times at three-week intervals hydroxide (placebo) before they infected BA.1. Neutralizing antibody (nAB) titers, weight, lung symptoms, viral loads, as measured RT-PCR upper lower respiratory tracts, determined. addition, infectious titers lungs plaque-forming assay. found that W-PreS-O-vaccinated developed robust nABs against BA.1, showed almost no development pneumonia, had significantly reduced lungs. Importantly, loads nasal cavities close above PCR cycle threshold considered be non-infectious. data our proof-of-concept provides compelling evidence has protective effect hamster vivo infection model thus support promising results obtained also for other

Language: Английский

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New insights into human immune memory from SARS‐CoV‐2 infection and vaccination

Allergy, Journal Year: 2022, Volume and Issue: 77(12), P. 3553 - 3566

Published: Sept. 1, 2022

Abstract Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting mass morbidity estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique innovative means to identify infected individuals, technologies evaluate immune responses infection vaccination, new therapeutic strategies treat individuals. Never before immunology so critically at forefront of combatting a global pandemic. It now become evident that not just antibody responses, but formation durability memory cells following vaccination are associated protection against severe disease from infection. Furthermore, emergence concern (VoC) highlight need for immunological markers quantify protective capacity Wuhan‐based vaccines. Thus, harnessing modulating response is key successful treatment disease. We here review latest knowledge about generation natural provide insights into attributes may protect variants.

Language: Английский

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Vaccine Based on Recombinant Fusion Protein Combining Hepatitis B Virus PreS with SARS-CoV-2 Wild-Type- and Omicron-Derived Receptor Binding Domain Strongly Induces Omicron-Neutralizing Antibodies in a Murine Model

Vaccines, Journal Year: 2024, Volume and Issue: 12(3), P. 229 - 229

Published: Feb. 23, 2024

Background: COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a recurrent endemic disease affecting whole world. Since November 2021, Omicron and its subvariants have dominated in spread of disease. In order to prevent courses disease, vaccines are needed boost maintain antibody levels capable neutralizing Omicron. Recently, we produced characterized SARS-CoV-2 vaccine based on recombinant fusion protein consisting hepatitis B virus (HBV)-derived PreS two wild-type RBDs. Objectives: To develop PreS-RBD which induces high Omicron-specific antibodies. Methods: We designed, produced, compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix W-PreS-W O-PreS-O) chimeric (i.e., W-PreS-O) subunit vaccines. Immunogens were vitro using chemical methods, mass spectrometry, circular dichroism combination with thermal denaturation immunological methods. addition, BALB/c mice immunized aluminum–hydroxide-adsorbed proteins aluminum hydroxide alone placebo) study specific cytokine responses, safety neutralization. Results: Defined pure immunogens could be significant quantities as secreted folded mammalian cells. The antibodies induced after vaccination different doses strain-specific, reacted RBD dose-dependent manner resulted mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG comparable, but W-PreS-O-induced neutralization titers against (median VNT50: 5000) seven- twofold higher than W-PreS-W- O-PreS-O-specific ones, respectively, they six-fold those vaccine. Conclusion: Among tested immunogens, vaccine, W-PreS-O, highest Thus, W-PreS-O seems highly promising COVID-19 candidate for further preclinical clinical evaluation.

Language: Английский

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