Epitope Analysis of Anti-SARS-CoV-2 Neutralizing Antibodies

Xue, Jun‐biao; Tao, Sheng-Ce

doi:10.1007/s11596-021-2453-8

Cited by 3 publications

(4 citation statements)

References 72 publications

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“…According to the published works and determined complexes, NAbs target SARS-CoV-2 with various conformations and neutralization mechanisms. These NAbs can be divided into five types (type 1 to type 5) based on different epitopes they target (38). Table 3 shows the five types of antibodies and the neutralization mechanisms of them.…”

Section: Case Studymentioning

confidence: 99%

A Structure-Based B-cell Epitope Prediction Model Through Combing Local and Global Features

Lü

et al. 2022

Front. Immunol.

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B-cell epitopes (BCEs) are a set of specific sites on the surface of an antigen that binds to an antibody produced by B-cell. The recognition of BCEs is a major challenge for drug design and vaccines development. Compared with experimental methods, computational approaches have strong potential for BCEs prediction at much lower cost. Moreover, most of the currently methods focus on using local information around target residue without taking the global information of the whole antigen sequence into consideration. We propose a novel deep leaning method through combing local features and global features for BCEs prediction. In our model, two parallel modules are built to extract local and global features from the antigen separately. For local features, we use Graph Convolutional Networks (GCNs) to capture information of spatial neighbors of a target residue. For global features, Attention-Based Bidirectional Long Short-Term Memory (Att-BLSTM) networks are applied to extract information from the whole antigen sequence. Then the local and global features are combined to predict BCEs. The experiments show that the proposed method achieves superior performance over the state-of-the-art BCEs prediction methods on benchmark datasets. Also, we compare the performance differences between data with or without global features. The experimental results show that global features play an important role in BCEs prediction. Our detailed case study on the BCEs prediction for SARS-Cov-2 receptor binding domain confirms that our method is effective for predicting and clustering true BCEs.

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Section: Case Studymentioning

confidence: 99%

A Structure-Based B-cell Epitope Prediction Model Through Combing Local and Global Features

Lü

et al. 2022

Front. Immunol.

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“…Compared to the trimer 2 conformation, one would expect that among antibodies generated against the trimer 1 conformation, a greater number would recognize epitopes in the S2 subunit. Most neutralizing antibodies that have been characterized, however, recognize epitopes in the S1 subunit, primarily in the RBD and NTD, and antibodies recognizing S2 epitopes are frequently weaker neutralizers than those recognizing S1 epitopes 36 , 37 . Olia et al reported lower titers of neutralizing antibodies when mice were inoculated with “aged” spike preparations that would be expected to contain largely trimer 1-like conformations 29 .…”

Section: Discussionmentioning

confidence: 99%

Influence of variant-specific mutations, temperature and pH on conformations of a large set of SARS-CoV-2 spike trimer vaccine antigen candidates

Stuible,

Schrag,

Sheff

et al. 2023

Sci Rep

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SARS-CoV-2 subunit vaccines continue to be the focus of intense clinical development worldwide. Protein antigens in these vaccines most commonly consist of the spike ectodomain fused to a heterologous trimerization sequence, designed to mimic the compact, prefusion conformation of the spike on the virus surface. Since 2020, we have produced dozens of such constructs in CHO cells, consisting of spike variants with different mutations fused to different trimerization sequences. This set of constructs displayed notable conformational heterogeneity, with two distinct trimer species consistently detected by analytical size exclusion chromatography. A recent report showed that spike ectodomain fusion constructs can adopt an alternative trimer conformation consisting of loosely associated ectodomain protomers. Here, we applied multiple biophysical and immunological techniques to demonstrate that this alternative conformation is formed to a significant extent by several SARS-CoV-2 variant spike proteins. We have also examined the influence of temperature and pH, which can induce inter-conversion of the two forms. The substantial structural differences between these trimer types may impact their performance as vaccine antigens.

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“…In fact, there are two classifications of neutralizing antibodies based on the RBD structural recognition and their capacity to block the RBD:hACE-2 interaction. The first classification identifies four types (I–IV) [ 86 ] of neutralizing antibodies, whereas the second one identifies five types (I–V) [ 87 ]. Both classifications are similar, with the latter adding type V, which entails antibodies that recognize non-RBD SARS-CoV-2 regions, including other proteins, such as NTD and S2.…”

Section: Interaction Of the Therapeutic Antibodies With The Rbdmentioning

confidence: 99%

“…Class I antibodies recognize a conserved orientation of the RBM only in the “up” state conformation [ 88 , 89 ]. These antibodies are mostly derived from IGHV3 and IGHV1 gene families, including germline genes IGHV3-53, IGHV3-30, IGHV3-33, IGHV3-66, IGHV1-58, and IGHV1-18 [ 87 ]. Most of the therapeutic antibodies belong to this class, with four out of the nine antibodies (44%): Casirivimab, Etesevimab, Tixagevimab, and Regdanvimab ( Table 3 ).…”

Section: Interaction Of the Therapeutic Antibodies With The Rbdmentioning

confidence: 99%

Evolution of Anti-SARS-CoV-2 Therapeutic Antibodies

Almagro

Mellado-Sánchez

Pedraza-Escalona

et al. 2022

IJMS

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Since the first COVID-19 reports back in December of 2019, this viral infection caused by SARS-CoV-2 has claimed millions of lives. To control the COVID-19 pandemic, the Food and Drug Administration (FDA) and/or European Agency of Medicines (EMA) have granted Emergency Use Authorization (EUA) to nine therapeutic antibodies. Nonetheless, the natural evolution of SARS-CoV-2 has generated numerous variants of concern (VOCs) that have challenged the efficacy of the EUA antibodies. Here, we review the most relevant characteristics of these therapeutic antibodies, including timeline of approval, neutralization profile against the VOCs, selection methods of their variable regions, somatic mutations, HCDR3 and LCDR3 features, isotype, Fc modifications used in the therapeutic format, and epitope recognized on the receptor-binding domain (RBD) of SARS-CoV-2. One of the conclusions of the review is that the EUA therapeutic antibodies that still retain efficacy against new VOCs bind an epitope formed by conserved residues that seem to be evolutionarily conserved as thus, critical for the RBD:hACE-2 interaction. The information reviewed here should help to design new and more efficacious antibodies to prevent and/or treat COVID-19, as well as other infectious diseases.

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Epitope Analysis of Anti-SARS-CoV-2 Neutralizing Antibodies

Cited by 3 publications

References 72 publications

A Structure-Based B-cell Epitope Prediction Model Through Combing Local and Global Features

A Structure-Based B-cell Epitope Prediction Model Through Combing Local and Global Features

Influence of variant-specific mutations, temperature and pH on conformations of a large set of SARS-CoV-2 spike trimer vaccine antigen candidates

Evolution of Anti-SARS-CoV-2 Therapeutic Antibodies

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