Mucosal immune response in biology, disease prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 7, 2025

Abstract The mucosal immune system, as the most extensive peripheral network, serves frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion establishing tolerance. A comprehensive understanding immunity essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing overall impact on body. Despite its importance, our knowledge remains incomplete, necessitating further research. outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored critical role disease prevention treatment. This systematic review focuses dynamic interactions between mucosa-associated lymphoid structures related diseases. We delve into basic functions these tissues during processes explore intricate regulatory networks mechanisms involved. Additionally, we summarize novel therapies clinical research advances immunity-related also addresses challenges vaccines, which aim to induce specific responses while maintaining tolerance non-pathogenic microbes. Innovative therapies, such nanoparticle vaccines inhalable antibodies, show promise enhancing offer potential improved

Language: Английский

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Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses

Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112271 - 112271

Published: March 7, 2023

In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led rapid succession sub-lineages with waves BA.2 BA.4/5 infection. Recently, many variants have such as BQ.1 XBB, which carry up 8 additional receptor-binding domain (RBD) amino acid substitutions compared BA.2. We describe panel 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering breakthrough infections. Epitope mapping shows mAb binding shifting 3 clusters, corresponding early-pandemic hotspots. The RBD mutations in recent map close these sites knock out severely down neutralization activity all but 1 mAb. This corresponds large falls titer vaccine BA.2, immune serum.

Language: Английский

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Multiplexed discrimination of SARS-CoV-2 variants via plasmonic-enhanced fluorescence in a portable and automated device

Nature Biomedical Engineering, Journal Year: 2023, Volume and Issue: 7(12), P. 1636 - 1648

Published: Sept. 21, 2023

Language: Английский

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The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 28, 2024

Abstract Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to failure of all mAbs developed clinical use. Most potent bind receptor binding domain which heavily mutated. Here we study responses conserved epitope in sub-domain-1 (SD1) have more prominent because mutational escape directed domain. Some SD1 reactive show and broad neutralization variants. We structurally map dominant provide mechanism action blocking interaction with ACE2. Mutations not been sustained date, but one, E554K, leads mAbs. This mutation now emerged several sublineages including BA.2.86, reflecting selection on virus exerted increasing prominence anti-SD1 response.

Language: Английский

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Reaction Pathway Differentiation Enabled Fingerprinting Signal for Single Nucleotide Variant Detection

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Accurate identification of single‐nucleotide variants (SNVs) is paramount for disease diagnosis. Despite the facile design DNA hybridization probes, their limited specificity poses challenges in clinical applications. Here, a differential reaction pathway probe (DRPP) based on dynamic network presented. DRPP leverages differences intermediate concentrations between SNV and WT groups, directing them into distinct pathways. This generates strong pulse‐like signal weak unidirectional increase wild‐type (WT). Through application machine learning to fluorescence kinetic data analysis, classification signals automated with an accuracy 99.6%, significantly exceeding 80.7% conventional methods. Additionally, sensitivity variant allele frequency (VAF) enhanced down 0.1%, representing ten‐fold improvement over approaches. accurately identified D614G N501Y SNVs S gene SARS‐CoV‐2 patient swab samples 99% (n = 82). It determined VAF ovarian cancer‐related mutations KRAS‐G12R , NRAS‐G12C BRAF‐V600E both tissue blood 77), discriminating cancer patients healthy individuals significant difference ( p < 0.001). The potential integration diagnostics, along rapid amplification techniques, holds promise early diagnostics personalized diagnostics.

Language: Английский

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Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 29, 2024

The rapid emergence and global dissemination of the Omicron variant SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores urgent need for an enhanced understanding Omicron's pathophysiological mechanisms to guide clinical management shape health strategies. Our study is aimed at deciphering intricate molecular underlying infections, particularly focusing on identification specific biomarkers.

Language: Английский

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Shared IGHV1-69-encoded neutralizing antibodies contribute to the emergence of L452R substitution in SARS-CoV-2 variants

Emerging Microbes & Infections, Journal Year: 2022, Volume and Issue: 11(1), P. 2749 - 2761

Published: Oct. 26, 2022

SARS-CoV-2 variants continue to emerge facing established herd immunity. L452R, previously featured in the Delta variant, quickly emerged Omicron subvariants, including BA.4/BA.5, implying a continued selection pressure on this residue. The underlying links between spike mutations and their selective pressures remain incompletely understood. Here, by analyzing 221 structurally characterized antibodies, we found that IGHV1-69-encoded antibodies preferentially contact L452 using germline-encoded hydrophobic residues at tip of HCDR2 loop. Whereas somatic hypermutations or VDJ rearrangements are required acquire L452-contacting for non-IGHV1-69 encoded antibodies. Antibody repertoire analysis revealed IGHV1-69 antibody lineages commonly induced among COVID-19 convalescents but exhibit limited prevalence. In addition, experimentally demonstrated L452R renders most published ineffective. Furthermore, enriched experienced BA.1 (without L452R) breakthrough infections rarely (with infections. Taken together, these findings support population contribute substitution. This study thus provides better understanding variant genesis immune evasion.

Language: Английский

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Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 24, 2023

SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier the pandemic. Investigation of memory B cells from patients primarily breakthrough infections Delta variant enables isolation a number neutralizing cross-reactive to heterologous concern (VOCs) including (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and unusual heavy chain CDR2 insertions respectively two representative cross-neutralizing antibodies-YB9-258 YB13-292. These features are putatively introduced by somatic hypermutation they heavily involved epitope recognition broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral except those induced HIV-1 chronic infections. data provide molecular mechanisms cross-neutralization infected implications future vaccination strategy.

Language: Английский

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Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes

Life Science Alliance, Journal Year: 2023, Volume and Issue: 6(9), P. e202201796 - e202201796

Published: July 4, 2023

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, open. S-trimers adopting locked are tightly packed featuring structural elements incompatible with RBD in the “up” position. For S, it shown transient under neutral pH. Probably because their transience, remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, x3 disulfides into Some these have preserve rare when Introduction allowed us image other S cryo-EM. We identified bound cofactors features associated conformations. compare newly determined structures available SARS-related CoVs identify conserved discuss possible functions.

Language: Английский

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Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 11, 2024

Abstract In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe–critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 and 1,067 placebo recipients who acquired this set of prespecified analyses, we show that in Latin America, VE significantly lower Lambda vs. Reference non-Lambda [family-wise error rate (FWER) p < 0.05]. differed by residue match mismatch vaccine-insert at 16 amino acid positions (4 FWER 0.05; 12 q-value ≤ 0.20); decreased with physicochemical-weighted Hamming distance vaccine-strain sequence for Spike, receptor-binding domain, N-terminal S1 (FWER 0.001); 0.05) strain measured 9 antibody-epitope escape scores 4 NTD neutralization-impacting features; (p = 0.011) neutralization resistance level vaccinee sera. COVID-19 stable across most features but distant viruses.

Language: Английский

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