Recent developments in the immunopathology of COVID‐19

Allergy, Journal Year: 2022, Volume and Issue: 78(2), P. 369 - 388

Published: Nov. 24, 2022

Abstract There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID‐19) patients during pandemic thanks to extensive vaccination programs. Here, we highlight recent studies on COVID‐19, from immunological protective risk factors for severity mortality COVID‐19. The efficacy COVID‐19 vaccines potential allergic reactions after administration are also discussed. occurrence new variants concerns such as Omicron BA.2, BA.4, BA.5 global have changed scenario Multisystem inflammatory syndrome children (MIS‐C) may cause severe heterogeneous but with a lower rate. Perturbations immunity T cells, B mast well autoantibodies metabolic reprogramming contribute long‐term symptoms is conflicting evidence about whether atopic diseases, asthma rhinitis, associated susceptibility better outcomes At beginning pandemic, European Academy Allergy Clinical Immunology (EAACI) developed guidelines that provided timely information management diseases preventive measures reduce transmission clinics. distribution emerging acute respiratory coronavirus 2 (SARS‐CoV‐2) reduced pathogenic dramatically decreased morbidity, severity, Nevertheless, breakthrough infection remains challenge control. Hypersensitivity (HSR) low compared other vaccines, these were addressed EAACI statements indications reactions, including anaphylaxis vaccines. We gained depth knowledge experience over years since start yet full eradication SARS‐CoV‐2 not horizon. Novel strategies warranted prevent high‐risk groups, development MIS‐C long

Language: Английский

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Differential decline of SARS‐CoV‐2‐specific antibody levels, innate and adaptive immune cells, and shift of Th1/inflammatory to Th2 serum cytokine levels long after first COVID‐19

Allergy, Journal Year: 2024, Volume and Issue: 79(9), P. 2482 - 2501

Published: July 14, 2024

SARS-CoV-2 has triggered a pandemic and contributes to long-lasting morbidity. Several studies have investigated immediate cellular humoral immune responses during acute infection. However, little is known about long-term effects of COVID-19 on the system.

Language: Английский

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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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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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Advances in SARS-CoV-2 receptor-binding domain-based COVID-19 vaccines

Expert Review of Vaccines, Journal Year: 2023, Volume and Issue: 22(1), P. 422 - 439

Published: May 10, 2023

Introduction The Coronavirus Disease 2019 (COVID-19) pandemic has caused devastating human and economic costs. Vaccination is an important step in controlling the pandemic. Severe acute respiratory coronavirus-2 (SARS-CoV-2), causative agent of COVID-19, infects cells by binding a cellular receptor through receptor-binding domain (RBD) within S1 subunit spike (S) protein. Viral entry membrane fusion are mediated S2 subunit.Areas covered SARS-CoV-2 S protein, particularly RBD, serves as target for vaccines. Here we review structure function protein its summarize current COVID-19 vaccines targeting outline potential strategies improving RBD-based Overall, this provides information that will facilitate rational design development safer more effective vaccines.Expert opinion harbors numerous mutations, mostly resulting multiple variant strains. Although many RBD original virus strain (and previous variants) can prevent infection these strains, their ability against recent dominant variants, Omicron offspring, significantly reduced. Collective efforts needed to develop broad-spectrum control future variants have potential.

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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Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine

EBioMedicine, Journal Year: 2023, Volume and Issue: 92, P. 104574 - 104574

Published: May 4, 2023

The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: emergence vaccine-resistant mutant viruses, vaccine stability during storage transport, waning vaccine-induced immunity, concerns about infrequent adverse events associated with existing vaccines.We report on a protein subunit comprising receptor-binding domain (RBD) ancestral spike protein, dimerised immunoglobulin IgG1 Fc domain. These were tested in conjunction three different adjuvants: TLR2 agonist R4-Pam2Cys, NKT cell glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats hamsters. We also developed RBD-human RBD sequence immuno-evasive beta variant (N501Y, E484K, K417N). as heterologous third dose booster following priming whole vaccine.Each formulation RBD-Fc drove strong neutralising antibody (nAb) responses provided durable highly protective immunity against lower upper airway infection mouse models COVID-19. 'beta variant' vaccine, combined induced protection mice strain well strain. Furthermore, when used booster, increased titres nAb other variants including alpha, delta, delta+, gamma, lambda, mu, omicron BA.1, BA.2 BA.5.These results demonstrated that subunit/MF59® adjuvanted can induce high levels broadly reactive nAbs, prior immunisation ancestral-strain vaccines. This platform offers potential approach to augment some currently approved face emerging concern, it now entered phase I clinical trial.This work was supported by grants from Medical Research Future Fund (MRFF) (2005846), Jack Ma Foundation, National Health Council Australia (NHMRC; 1113293) Singapore (MOH-COVID19RF-003). Individual researchers NHMRC Senior Principal Fellowship (1117766), Investigator Awards (2008913 1173871), Australian Discovery Early Career Award (ARC DECRA; DE210100705) philanthropic awards IFM investors A2 Milk Company.

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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Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 27, 2024

Background The house dust mite (HDM) is widely recognized as the most prevalent allergen in allergic diseases. Allergen-specific immunotherapy (AIT) has been successfully implemented clinical treatment for HDM. Hypoallergenic B-cell epitope-based vaccine designed by artificial intelligence (AI) represents a significant progression of recombinant hypoallergenic derivatives. Method three-dimensional protein structure Der f 36 was constructed using Alphafold2. AI-based tools were employed to predict epitopes, which subsequently verified through IgE-reaction testing. then synthesized, expressed, and purified. reduced allergenicity assessed enzyme-linked immunosorbent assay (ELISA), immunoblotting, basophil activation test. T-cell response evaluated based on cytokine expression peripheral blood mononuclear cells (PBMCs) patients. immunogenicity compared rabbit immunization with 36, respectively. inhibitory effect blocking IgG antibody specific IgE-binding activity also examined. Results final selected non-allergic epitopes 25–48, 57–67, 107–112, 142–151, 176–184. showed reduction activity. competitive inhibition investigated only 20% could be achieved, greatly when (98%). exhibited low basophil-stimulating ratio similar that negative control, it induce an increasing level IFN‐γ but not Th2 cytokines IL-5 IL-13 PBMCs. vaccine-specific antibodies inhibit patients’ IgE binding stimulation Derf 36. Conclusion This study first application AI strategy facilitate development vaccine, may become promising HDM-allergic patients due its high inducing IgG.

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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