Key mechanistic features of the trade-off between antibody escape and host cell binding in the SARS-CoV-2 Omicron variant spike proteins

The EMBO Journal, Год журнала: 2024, Номер 43(8), С. 1484 - 1498

Опубликована: Март 11, 2024

Abstract Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and the recently emerged BA.2.86 JN.1. Receptor binding immune evasion are recognized as two major drivers for evolution of receptor domain (RBD) spike (S) protein. However, underlying mechanism interplay between factors remains incompletely understood. Herein, we determined structures human ACE2 complexed with XBB RBDs. Based on ACE2/RBD these sub-variants a comparison known complex structures, found that R346T substitution in RBD enhanced upon an interaction residue R493, but not Q493, via involving long-range conformation changes. Furthermore, R493Q F486V exert balanced impact, through which capability was somewhat compromised to achieve optimal binding. We propose “two-steps-forward one-step-backward” model describe such compromise affinity during sub-variants.

Язык: Английский

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Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2

The Journal of Immunology, Год журнала: 2025, Номер 214(1), С. 115 - 129

Опубликована: Янв. 1, 2025

Abstract As one of the earliest identified susceptible animals for SARS-CoV-2, cats are also vulnerable hosts feline coronaviruses, ie enteric coronavirus (FECV). Here, to understand cross-presentation coronavirus-derived peptides by cat major histocompatibility complex molecule leucocyte antigen (FLA) class I, unpredictable natural peptide motifs presented FLA-K*00701 and FLA-E*00301 were through elution further confirmed structural determination 2 FLA I molecules. Based on these precise peptides, atlas cross-presenting from different coronaviruses in sketched with 3 hotspots C-terminal half ORF1ab protein. The possibility is supported similar conformation corresponding KP-CoV-9 (RSFIEDLLF) KM-FECV-9 (RSAVEDLLF) FLA-K*00701. Our findings provide insights into understanding SARS-CoV-2 FECV development universal vaccine coronaviruses.

Язык: Английский

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Elevated hyaluronic acid levels in severe SARS-CoV-2 infection in the post-COVID-19 era

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Фев. 8, 2024

Objective Human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promoted the coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA) via NamiRNA-enhancer network, based on previous experimental research. This study aimed to investigate predictive value HA for severity SARS-CoV-2 infection in post-COVID-19 era. Methods A total 217 consecutive patients with COVID-19 were enrolled at Beijing Ditan Hospital between July 2023 and October 2023. levels analyzed using biochemical detector. Logistic regression analysis was used screen independent factors COVID-19. The performance assessed ROC curve. Furthermore, relationship investigated multivariate logistic models after adjustment potential confounders. Results According cut-off HA, divided into < 90 ng/mL group (80 cases) ≥ (137 cases). High positively associated infection, including elevated inflammatory indicators, lung involvement, prolonged clinical course, higher incidence failure death (P 0.05). suggested that an predictor (OR = 4.540, 95% CI 2.105-9.790, P 0.001). curve showed AUC 0.724. significantly cases compared healthy population (123.9 (82.6, 174.1) vs. 50.5 (37.8, 66.8), 0.001), but similar those non-SARS-CoV-2 (121.6 (78.5, 175.6) 106.0 (66.5, 149.7), 0.244). We also found first infections had (118.8 (79.5, 174.3) 85.0 (61.1, 128.8), 0.001) a proportion (37.1% 21.3%, 0.043) than re-infections. However, expression failed fully return normal recovery (204.7 (152.9, 242.2) 97.0 (69.3, 137.3), Conclusion could be as novel serum biomarker predict risk

Язык: Английский

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Revisiting the dimensions of universal vaccine with special focus on COVID-19: Efficacy versus methods of designing

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 277, С. 134012 - 134012

Опубликована: Июль 22, 2024

Язык: Английский

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Antibody levels versus vaccination status in the outcome of older adults with COVID-19

JCI Insight, Год журнала: 2024, Номер 9(20)

Опубликована: Окт. 22, 2024

BACKGROUNDDespite the currently prevailing, milder Omicron variant of COVID-19, older adults remain at elevated risk hospital admission, critical illness, and death. Loss efficacy immune system, including reduced strength, quality, durability antibody responses, may render generalized recommendations on booster vaccinations inadequate. There is a lack data levels in utility vaccination status versus as correlate protection. It further unclear whether be used to guide timing adults.METHODSWe conducted prospective multicenter cohort study comprising hospitalized patients with COVID-19. Anti-SARS-CoV-2 spike antibodies were measured admission. The primary endpoint was in-hospital mortality. Patients stratified by age, levels, status. Multiple logistic regression Cox analyses conducted.RESULTSIn total, 785 (≥60 years age [a]) 367 controls (<60a) included. After adjusting for confounders, mortality, ICU endotracheal intubation, oxygen administration 4.9, 2.6, 6.5, 2.3 times higher, respectively, if < 1,200 BAU/mL (aOR, 4.92 [95%CI, 2.59-9.34], P 0.0001; aOR, 2.64 1.52-4.62], = 0.0006; 6.50 1.48-28.47], 0.013; 2.34 1.60-3.343], 0.0001). Older infected approximately 6 more likely die 6.3 [95% CI, 2.43-16.40], 0.0002).CONCLUSIONAntibody stronger predictor mortality than Monitoring constitute better direct approach safeguarding from adverse COVID-19 outcomes.

Язык: Английский

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Uncommon P1 Anchor-featured Viral T Cell Epitope Preference within HLA-A*2601 and HLA-A*0101 Individuals

ImmunoHorizons, Год журнала: 2024, Номер 8(6), С. 415 - 430

Опубликована: Июнь 1, 2024

Abstract The individual HLA-related susceptibility to emerging viral diseases such as COVID-19 underscores the importance of understanding how HLA polymorphism influences peptide presentation and T cell recognition. Similar HLA-A*0101, which is one earliest identified alleles among human population, HLA-A*2601 possesses a similar characteristic for binding acts prevalent allomorph in HLA-I. In this study, we found that, compared with individuals exhibit distinctive features responses SARS-CoV-2 influenza virus after infection and/or vaccination. heterogeneous can be attributed distinct preference HLA-A*0101 epitope motifs negative-charged residues at P1 P3 positions, respectively. Furthermore, determined crystal structures complexed four peptides derived from papillomavirus, structure comparison. shallow pocket C results promiscuous “switchable” bulged conformations because secondary anchor median portion. Notably, hydrogen bond network formed between anchors HLA-A*2601-specific lead “closed” conformation solid placement accommodation A. This insight sheds light on intricate relationship I allelic allomorphs, binding, immune response provides valuable implications disease potential vaccine design.

Язык: Английский

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Boosting PRRSV-Specific Cellular Immunity: The Immunological Profiling of an Fc-Fused Multi-CTL Epitope Vaccine in Mice

Veterinary Sciences, Год журнала: 2024, Номер 11(6), С. 274 - 274

Опубликована: Июнь 15, 2024

The continuously evolving PRRSV has been plaguing pig farms worldwide for over 30 years, with conventional vaccines suffering from insufficient protection and biosecurity risks. To address these challenges, we identified 10 PRRSV-specific CTL epitopes through enzyme-linked immunospot assay (ELISPOT) constructed a multi-epitope peptide (PTE) by linking them in tandem. This PTE was then fused modified porcine Fc molecule to create the recombinant protein pFc-PTE. Our findings indicate that pFc-PTE effectively stimulates PRRSV-infected specific splenic lymphocytes secrete high levels of interferon-gamma (IFN-γ) is predicted be non-toxic non-allergenic. Compared alone, not only induced comparable cellular immune response mice but also extended duration at least weeks post-immunization. Additionally, predominantly Th1 response, suggesting its potential advantage enhancing immunity. Consequently, holds promise as novel, safe, potent candidate vaccine may provide new perspectives design against other viral diseases.

Язык: Английский

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Interplay of inflammatory markers and anti-SARS-CoV-2 antibodies in COVID-19 mortality: A prospective cohort study

International Journal of Infectious Diseases, Год журнала: 2024, Номер 143, С. 107016 - 107016

Опубликована: Март 22, 2024

Despite high global vaccination coverage, it remains unclear how and anti-SARS-CoV-2 antibodies affect immune responses inflammation levels in patients with COVID-19. It is further whether the inflammatory response differs depending on antibody combination of COVID-19 affects mortality rates.

Язык: Английский

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Biosafety and immunology: An interdisciplinary field for health priority

Biosafety and Health, Год журнала: 2024, Номер 6(5), С. 310 - 318

Опубликована: Июль 14, 2024

Biosafety hazards can trigger a host immune response after infection, invasion, or contact with the host. Whether infection microorganism results in disease biosafety concerns depends to large extent on status of population. Therefore, it is essential investigate immunological characteristics and mechanisms biological threats agents protect more effectively. Emerging re-emerging infectious diseases, such as current coronavirus 2019 (COVID-19) pandemic, have raised regarding both immunology worldwide. Interdisciplinary studies involved are relevant many fields, including development vaccines other interventions monoclonal antibodies T-cells, herd immunity (or population-level barrier immunity), immunopathology, multispecies immunity, i.e., animals even plants. Meanwhile, advances science technology occurring rapidly, resulting important research achievements that may contribute recognition emerging hazards, well early warning, prevention, defense systems. This review provides an overview interdisciplinary field immunology. Close collaboration innovative application becoming for human health.

Язык: Английский

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Anti-SARS-CoV-2 Antibodies versus Vaccination Status in CAD Patients with COVID-19: A Prospective, Propensity Score-Matched Cohort Study

Vaccines, Год журнала: 2024, Номер 12(8), С. 855 - 855

Опубликована: Июль 30, 2024

Despite the currently prevailing, milder Omicron variant, coronary artery disease (CAD) patients constitute a major risk group in COVID-19, exhibiting 2.6 times mortality of non-CAD and representing over 22% non-survivors. No data are available on efficacy antibody levels CAD patients, nor relevance vaccination status versus for predicting severe courses COVID-19 mortality. Nor there definitive indicators to assess if individual sufficiently protected from adverse outcomes or determine necessity booster vaccinations.

Язык: Английский

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