Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-COV-2 Variants

Опубликована: Апрель 10, 2024

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories broadly neutralizing antibodies (bnAbs) that retain prominent against emerging variants sub-lineages. molecular characteristics, epitope conservation, resistance mechanisms these are further detailed, aiming to offer suggestion or direction for therapeutic antibodies, facilitate vaccine design with broad-spectrum potential.

Язык: Английский

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Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-CoV-2 Variants

Viruses, Год журнала: 2024, Номер 16(6), С. 900 - 900

Опубликована: Июнь 1, 2024

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories broadly neutralizing antibodies (bnAbs) that retain prominent against emerging variants sub-lineages. molecular characteristics, epitope conservation, resistance mechanisms these are further detailed, aiming to offer suggestion or direction for therapeutic antibodies, facilitate design with broad-spectrum potential.

Язык: Английский

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Rethinking Optimal Immunogens to Face SARS‐CoV‐2 Evolution Through Vaccination

Influenza and Other Respiratory Viruses, Год журнала: 2025, Номер 19(1)

Опубликована: Янв. 1, 2025

ABSTRACT SARS‐CoV‐2, which originated in China late 2019, quickly fueled the global COVID‐19 pandemic, profoundly impacting health and economy worldwide. A series of vaccines, mostly based on full SARS‐CoV‐2 Spike protein, were rapidly developed, showing excellent humoral cellular responses high efficacy against both symptomatic infection severe disease. However, viral evolution waning neutralizing strongly challenged vaccine long term effectiveness, mainly infection, making necessary a strategy repeated updated booster shots. In this vaccination context, antibody repertoire diversification was evidenced, although immune imprinting after doses or reinfection also demonstrated identified as major determinant immunological to antigen exposures. Considering that small domain receptor binding (RBD), is target antibodies concentrates most mutations, following text aims provide insights into ongoing debate over best strategies for boosters. We address relevance developing new vaccines evolving RBD, thus focusing relevant antigenic sites variants. combination with immunofusing computerized approaches could minimize imprinting, therefore optimizing efficacy.

Язык: Английский

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Structural Immunology of SARS‐CoV‐2

Immunological Reviews, Год журнала: 2024, Номер unknown

Опубликована: Дек. 27, 2024

The SARS-CoV-2 spike (S) protein has undergone significant evolution, enhancing both receptor binding and immune evasion. In this review, we summarize ongoing efforts to develop antibodies targeting various epitopes of the S protein, focusing on their neutralization potency, breadth, escape mechanisms. Antibodies receptor-binding site (RBS) typically exhibit high neutralizing potency but are frequently evaded by mutations in variants. contrast, conserved regions, such as S2 stem helix fusion peptide, broader reactivity generally lower potency. However, several broadly have demonstrated exceptional efficacy against emerging variants, including latest omicron subvariants, underscoring potential vulnerable sites RBS-A RBS-D/CR3022. We also highlight public classes different protein. targeted present opportunities for germline-targeting vaccine strategies. Overall, developing escape-resistant, potent effective vaccines remains crucial combating future This review emphasizes importance identifying key utilizing antibody affinity maturation inform therapeutic design.

Язык: Английский

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Anti-SARS-CoV-2 serology based on ancestral RBD antigens does not correlate with the presence of neutralizing antibodies against Omicron variants

Microbiology Spectrum, Год журнала: 2024, Номер 13(1)

Опубликована: Ноя. 20, 2024

ABSTRACT Neutralizing antibody titers and binding levels are considered correlates of protection against severe SARS-CoV-2 infection. The clinical utility serology should be reevaluated in light the emergence escape variants, as commercial antibody-binding assays have not been adapted to virus’ antigenic evolution. We compared anti-SARS-CoV-2 four quantitative serological tests based on variable ancestral spike antigens (three in-house ELISAs prototype VIDAS IgG QUANT assay) neutralization pseudotyped Wuhan, BA.2, BA.4/5, BQ.1.1, XBB.1.1 viruses a cohort 100 patients infected 2020 or during Omicron waves. Binding correlated well with neutralizing for but association decreased BQ.1.1 XBB.1 (for assay, Spearman’s correlation was 0.82 [95% CI 0.74–0.88] 0.61 [0.46–0.72] BA.2 XBB.1, respectively). In 15% no antibodies assay still yielded ranging from 74 7,652 units/mL. Using an adjusted threshold receiver operating characteristic (ROC) curve analysis, specificity detection increased 0.15 (95% 0.02–0.45) 0.17 (0.04–0.41) 0.92 (0.64–1.00) 0.83 (0.59–0.96) respectively. Serological receptor-binding domain virus fail predict activity latest circulating variants. Adapting may improve their immunocompromised patients. IMPORTANCE Anti-SARS-CoV-2 developed response COVID-19 pandemic diagnose infection monitor individual’s immunity following natural vaccination. Given relationship between infection, many studies evaluated pre-Omicron era. An important potential use serology, which explores antibodies, is estimating level new particularly immunosuppressed individuals those at risk COVID. However, era, evade induced by previous infections vaccination, determined re-examined order determine whether these optimized adapting strains.

Язык: Английский

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Broad sarbecovirus neutralization by combined memory B cell antibodies to ancestral SARS-CoV-2

iScience, Год журнала: 2024, Номер 27(7), С. 110354 - 110354

Опубликована: Июнь 22, 2024

Antibodies play a pivotal role in protecting from SARS-CoV-2 infection, but their efficacy is challenged by the continuous emergence of viral variants. In this study, we describe two broadly neutralizing antibodies cloned memory B cells single convalescent individual after infection with ancestral SARS-CoV-2. Cv2.3194, resilient class 1 anti-RBD antibody, remains active against Omicron sub-variants up to BA.2.86. Cv2.3132, near pan-Sarbecovirus neutralizer, targets heptad repeat 2 membrane proximal region. When combined, Cv2.3194 and Cv2.3132 form complementary antibody cocktail exhibiting local dose-dependent synergy. Thus, remarkably robust cell elicited response can withstand evolution immune escape. The cooperative effect such combination may confer certain level protection latest

Язык: Английский

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Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches

Emerging Microbes & Infections, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 25, 2024

Unlocking the potential of broadly reactive coronavirus monoclonal antibodies (mAbs) and their derivatives offers a transformative therapeutic avenue against severe COVID-19, especially crucial for safeguarding high-risk populations. Novel mAb-based immunotherapies may help address reduced efficacy current vaccines neutralizing mAbs caused by emergence variants concern (VOCs). Using phage display technology, we discovered pan-SARS-CoV-2 mAb (C10) that targets conserved region within receptor-binding domain (RBD) virus. Noteworthy, C10 demonstrates exceptional in recognizing all assessed VOCs, including recent Omicron variants. While lacks direct neutralization capacity, it efficiently binds to infected lung epithelial cells induces lysis via natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Building upon this mAb, engineered C10-based, Chimeric Antigen Receptor (CAR)-T endowed with efficient killing capacity SARS-CoV-2-infected cells. Notably, NK CAR-T-cell mediated effectively reduces viral titers. These findings highlight non-neutralizing providing immune protection emerging infectious diseases. Our work reveals effective targeting proof-of-concept application CAR-T cell therapy combating SARS-CoV-2 infections. Furthermore, holds promise development innovative antibody-based cell-based strategies COVID-19 expanding array options available populations.Trial registration: ClinicalTrials.gov identifier: NCT04093596.

Язык: Английский

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Potent neutralization by a receptor binding domain monoclonal antibody with broad specificity for SARS-CoV-2 JN.1 and other variants

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 29, 2024

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. While increasing herd immunity, current vaccines, therapeutics have improved outcomes for some; prophylactic treatment interventions that are not compromised viral evolution the Spike protein still needed. Using rationally designed Receptor Binding Domain (RBD) - ACE2 fusion differential selection process with native Omicron RBD protein, we developed recombinant human monoclonal antibody (hmAb) from convalescent individual following infection. The hmAb, 1301B7 potently neutralized wide range variants including original Wuhan more recent JN.1 strain, as well SARS-CoV. Structure determination EG5.1 Spike/1301B7 Fab complex cryo-electron microscopy at 3.1Å resolution demonstrates contacts binding site exclusively through VH1-69 heavy chain, making using CDRs1-3, framework region 3 (FR3). Broad specificity is achieved many conserved residues Y501 H505. Consistent extensive epitope, able diminish burden in upper lower respiratory tract protect mice challenge XBB1.5 viruses. These results suggest has broad potential prevent or treat clinical infections guide development RBD-based universal vaccines therapeutic approaches.

Язык: Английский

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A potent, broadly neutralizing human monoclonal antibody that efficiently protects hACE2-transgenic mice from infection with the Wuhan, BA.5, and XBB.1.5 SARS-CoV-2 variants

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 19, 2024

The COVID-19 pandemic has uncovered the high genetic variability of SARS-CoV-2 virus and its ability to evade immune responses that were induced by earlier viral variants. Only a few monoclonal antibodies have been reported date are capable neutralizing broad spectrum Here, we report isolation new broadly human antibody, iC1. antibody was identified through sorting SARS-CoV-1 RBD-stained individual B cells isolated from blood vaccinated donor following breakthrough infection. In vitro , iC1 potently neutralizes pseudoviruses expressing wide range Spike variants, including those XBB sublineage. an hACE2-transgenic mouse model, provided effective protection against Wuhan strain as well BA.5 XBB.1.5 Therefore, can be considered potential component cocktails resisting mutation escape.

Язык: Английский

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Potent neutralization by a RBD antibody with broad specificity for SARS-CoV-2 JN.1 and other variants

npj Viruses, Год журнала: 2024, Номер 2(1)

Опубликована: Ноя. 14, 2024

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. By increasing herd immunity, current vaccines have improved infection outcomes for many. However, prophylactic treatment interventions that are not compromised viral evolution the Spike protein still needed. Using differential staining strategy with rationally designed Receptor Binding Domain (RBD) – ACE2 fusion native Omicron RBD protein, we developed recombinant human monoclonal antibody (hmAb) from convalescent individual following infection. The hmAb, 1301B7 potently neutralized wide range variants including original Wuhan-1, more recent JN.1 strain, SARS-CoV. contacts binding site exclusively through VH1-69 heavy chain. Broad specificity is achieved many conserved residues Y501 H505. Consistent extensive epitope, able diminish burden in upper lower respiratory tract protect mice challenge XBB1.5 viruses. These results suggest has broad potential prevent or treat clinical infections guide development RBD-based universal therapeutic approaches.

Язык: Английский

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