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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Neutralization of SARS‐CoV‐2 requires antibodies against conformational receptor‐binding domain epitopes

Allergy, Journal Year: 2021, Volume and Issue: 77(1), P. 230 - 242

Published: Aug. 28, 2021

Abstract Background The determinants of successful humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are critical importance for design effective vaccines and evaluation degree protective immunity conferred by exposure virus. As novel variants emerge, understanding their likelihood suppression population antibody repertoires has become increasingly important. Methods In this study, we analyzed SARS‐CoV‐2 polyclonal in a large clinically well‐characterized patients after mild COVID‐19 using panel microarrayed structurally folded unfolded proteins, as well sequential peptides, spanning surface spike protein (S) receptor‐binding domain (RBD) Results S‐ RBD‐specific responses were dominated immunoglobulin G (IgG), mainly IgG 1 , directed against S RBD three distinct peptide epitopes S2. virus neutralization activity patients´ sera was highly correlated with antibodies specific conformational but not ability prevent binding its human receptor angiotensin‐converting enzyme (ACE2). Twenty percent selectively lacked IgG. Only immunization folded, RBD, induced high virus‐neutralizing activity. Conformational required protection do seem be altered currently emerging variants. Conclusion These results fundamental estimating natural infection or vaccination vaccines, which can induce levels SARS‐CoV‐2–neutralizing conferring sterilizing immunity.

Language: Английский

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Evaluation of a commercial ELISA as alternative to plaque reduction neutralization test to detect neutralizing antibodies against SARS-CoV-2

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: March 3, 2022

Abstract High-throughput detection of neutralizing antibodies against SARS-CoV-2 presents a valuable tool for vaccine trials or investigations population immunity. We evaluate the performance first commercial surrogate virus neutralization test (sVNT, GenScript Biotech) plaque reduction (PRNT) in convalescent and vaccinated individuals. compare it to five other ELISAs, two which are designed detect antibodies. In 491 pre-vaccination serum samples, sVNT missed 23.6% PRNT-positive samples when using manufacturer-recommended cutoff 30% binding inhibition. Introducing an equivocal area between 15 35% maximized sensitivity specificity PRNT 72.8–93.1% 73.5–97.6%, respectively. The overall diagnostic ELISAs was below that sVNT. Vaccinated individuals exhibited higher antibody titers by (median 119.8, IQR 56.7–160) inhibition 95.7, 88.1–96.8) than patients 49.1, 20–62; median 52.9, 31.2–76.2). is suitable screen SARS-CoV-2-neutralizing antibodies; however, obtain accurate results, confirmatory testing required. This may require adaptation use individuals, due titers.

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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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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Natural human Bet v 1‐specific IgG antibodies recognize non‐conformational epitopes whereas IgE reacts with conformational epitopes

Allergy, Journal Year: 2023, Volume and Issue: 78(12), P. 3136 - 3153

Published: Sept. 13, 2023

Abstract Background The nature of epitopes on Bet v 1 recognized by natural IgG antibodies birch pollen allergic patients and pollen‐exposed but non‐sensitized subjects has not been studied in detail. Objective To investigate IgE recognition to study the effects 1‐specific 1‐induced basophil activation. Methods Sera from (BPA, n = 76), without allergy (NBPA, 40) non‐allergic individuals (NA, 48) were tested for IgE, as well 4 reactivity folded recombinant 1, two unfolded fragments comprising N‐terminal (F1) C‐terminal half (F2) peptides spanning corresponding sequences apple allergen Mal d ELISA or micro‐array analysis. ability serum inhibit binding rBet 1‐derivatives was assessed competition ELISAs. Furthermore, modulate activation investigated using rat basophilic leukaemia cells expressing human FcεRI which had loaded with BPA patients. Results react almost exclusively conformational whereas IgG, BPA, NBPA NA recognize mainly sequential epitopes. studies show that specific unfolded/sequential is inhibited hence latter seem represent cryptic did correlate therefore does be a result primary sensitization PR10 allergen‐containing food. Natural only poorly could even enhance Conclusion different These findings explain why allergen‐specific do protect against symptoms suggest have clonal origin.

Language: Английский

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Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS‐CoV‐2 vaccination

Allergy, Journal Year: 2022, Volume and Issue: 77(8), P. 2381 - 2392

Published: Feb. 6, 2022

Abstract Background Homologous and heterologous SARS‐CoV‐2 vaccinations yield different spike protein‐directed humoral cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods COV‐ADAPT is a prospective, observational cohort of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV‐19, BNT162b2 or nCoV‐19/BNT162b2. We assessed (anti‐spike‐RBD‐IgG, neutralizing antibodies, avidity) (spike‐induced T‐cell interferon‐γ release) responses in blood samples up 2 weeks before (T1) 2–12 following secondary immunization (T2). Results Initial nCoV‐19 resulted lower anti‐spike‐RBD‐IgG compared (70 ± 114 vs. 226 279 BAU/ml, p < .01) at T1. Booster proved superior T2 (anti‐spike‐RBD‐IgG: nCoV‐19/BNT162b2 2387 1627 3202 2184 413 461 both .001; spike‐induced release: 5069 6733 4880 7570 1152 2243 mIU/ml, .001). No significant differences were detected between BNT162b2‐boostered groups T2. For no booster effect on activation could be observed. found associations levels (ChAdOx1 BNT162b2) (homologous nCoV‐19/BNT162b2) from T1 Additionally, response linked time points (all combined). All regimes yielded antibodies increased antibody avidity Conclusions Interdependencies differ common regimes. unlikely compensate for poor

Language: Английский

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Omicron: A SARS‐CoV‐2 variant of real concern

Allergy, Journal Year: 2022, Volume and Issue: 77(5), P. 1616 - 1620

Published: Feb. 21, 2022

To the Editor, As of today (February 14, 2022), more than 410 million persons (https://coronavirus.jhu.edu/map.html) have reportedly been infected by SARS-CoV-2. Furthermore, mass production and global application COVID-19 vaccines begun (Supplemental reference S3). Both factors certainly contribute to fact, that although numbers worldwide SARS-CoV-2 infections end 2021 were double as high in 2020, number COVID-19-associated deaths has dropped approximately 50% at same time (https://coronavirus.jhu.edu/map.html). However, immunity which established so far is challenged appearance SARS-CoV-2-variants may escape cellular S4) antibody-dependent S5). The recently described variant concern (VOC) Omicron, emerged South Africa November 2021, spreading meantime rapidly all over world become a matter great because it shows changes genome affect compared with earlier variants1 references S6–S9). In particular, Omicron significantly amino acid mutations receptor-binding domain (RBD), binds ACE2 receptor on human cells, previous variants2 (Table S1). Antibodies directed RBD are critically important for virus-neutralization RBD-ACE2 interaction represents port entry virus into cells leading its replication host consecutive population.3, 4 ability RBD-specific antibodies prevent binding can be measured surrogate molecular assays,5 mimic classical tests3 therefore quickly adapted newly emerging variants using RBDs from corresponding variants. Here, we IgG recognition original Wuhan strain recent Delta (Pango B.1.617.2) B.1.1.529) S1) sera random sample adult convalescent patients S2: C1-C20) subjects vaccinated two times S3: D1-D10) or three T1-T10) registered vector- (i.e., Vaxzevria) and/or mRNA-based vaccine Comirnaty) (Figures 1 2; Table S4). studied these inhibit RBD-Wuhan, RBD-Delta, RBD-Omicron assay Gattinger et al.5 2, Sera had obtained April July 2020,3 43–92 days (median 57.5 days) after PCR confirmation infection, collected 26–31 27.5 days), samples 23–40 28 last vaccination, respectively (Tables S2 There no significant differences, regarding levels specific RBD-Wuhan S4: Median OD C1-C20: 0.385; D1-D10: 0.453; T1-T10: 2.339) RBD-Delta 0.379; 0.509; 2.470) S4, reduction comparing RBD-Delta: 4.3%), whereas RBD-Omicron-specific 0.073; 0.128; 0.836) lower those binding: 81.2%) (Figure 1A-C; agreement results inhibition serum 1D-F). inhibited stronger 1D). was not relevant manner who received immunizations much observed 87.8%) but did reach significance considerable Vaxzevria mounted S- twice Comirnaty 2). Lower induction Alpha neutralizing doses also noted another study.6 times, 27.7%) out ten T1, T3, showing less inhibition. Figure 2 antibody S, higher immunization, this difference Vaxzevria. immunized 2E-G). having third dose Comirnaty, 2D). Interestingly, median better treated 2xVaxzevria/1xComirnaty 2G) statistically significant. study if degree depending only other such specificity avidity antibodies7 play role, analyzed percentages parallel We found, certain (e.g., T1 relatively low IgG, accordingly, there T1) T3) ACE2. found T7, T8, T10) ACE This result together finding even enhanced >20% several 1D; C1, C2, C4, C5, C9, C11, C16, C17, C19, C20) would suggest, factors, thus form immune complexes7 well affinities/avidities their guide RBD-Omicron-ACE2 interaction.5, 7 we5 later others8 noticed contain seemed capable forming complexes RBD. Our current indicate occur vaccination. It possible S antigen produced genetic vaccination ratios then enhancement (ADE) disease side effects yet demonstrated. considered limitation our investigated responses assays limited subjects. supported very studies: One showed reduced neutralization convalescent/vaccinated subjects6 others variants.1, 9 provides additional information indicates cross-vaccination followed booster eventually provide slightly vaccinations further studies needed confirm this. summary, demonstrate recognized based Wuhan, when times. between ACE2, respectively. Omicron-induced severity seems due intrinsic features fact proportion population developed SARS-CoV-2-specific T cell S10) responses. re-infected large according attributed capacity receptor. SARS-CoV-2-protective shown drop quickly, now develop protective induced infection Therefore, appears real concern, especially vulnerable persons, will adapt strategies SARS-CoV- evolving achieved combination including most divergent inducing broad immunity. wish acknowledge help Doris Werjant-Locmele Anna Guentcheva recruitment administration grateful individuals participated study. Rudolf Valenta research grants HVD Life-Sciences, Vienna, Austria, WORG Pharmaceuticals, Hangzhou, China Viravaxx AG, Austria. He serves consultant AG Pharmaceuticals. authors conflict interest declare. PG: Designed performed experiments, data, wrote manuscript, read manuscript; IT, KB, AK: Performed provided clinical data; BK DT: WFP: Analyzed data RV: designed supervized experiments. Please note: publisher responsible content functionality any supporting supplied authors. Any queries (other missing content) should author article.

Language: Английский

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