Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Li, Tingting; Han, Xiaojian; Gu, Cheng; Guo, Hangtian; Zhang, Huajun; Wang, Ying‐Ming; Hu, Chao; Wang, Kai; Liu, Fengjiang; Luo, Feiyang; Zhang, Yanan; Hu, Jie; Wang, Wang; Li, Shenglong; Hao, Yanan; Shen, Meiying; Huang, Jingjing; Long, Yingyi; Song, Shuyi; Wu, Ruixue; Mu, Song; Chen, Qian; Gao, Feng; Wang, Jianwei; Long, Shunhua; Li, Luo; Wu, Yang; Gao, Yan; Xü, Wei; Cai, Xiujun; Qu, Di; Zhang, Zherui; Zhang, Hongqing; Li, Na; Gao, Qi; Zhang, Guiji; He, Chaojun; Wang, Wei; Ji, Xiaoyun; Tang, Ni; Yuan, Zhenghong; Xie, Youhua; Yang, Haitao; Zhang, Bo; Huang, Aiping; Jin, Aishun

doi:10.1038/s41467-021-26539-7

Cited by 48 publications

(58 citation statements)

References 45 publications

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“…Herein, we discussed the importance of the viral spike for the entry into the cell and focused on the effects of the point mutations on the binding affinity to the host receptor ACE2. However, it is important to stress that the viral spike, despite targeting the host for virus replication, also plays a major role in the infection resolution, by being blocked with the antibodies either generated by the human host defense system upon infection or after vaccination, or by therapeutic monoclonal antibodies [29,30]. Mutations occurring in the viral genome could result in the evolution of so-called 'escape variants'; some of these variants can show reduced susceptibility to antibodies [31,32].…”

Section: Resultsmentioning

confidence: 99%

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

2021

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The rise of SARS-CoV-2 variants, with changes that could be related to an increased virus pathogenicity, have received the interest of the scientific and medical community. In this study, we evaluated the changes that occurred in the viral spike of the SARS-CoV-2 Omicron variant and whether these changes modulate the interactions with the angiotensin-converting enzyme 2 (ACE2) host receptor. The mutations associated with the Omicron variant were retrieved from the GISAID and covariants.org databases, and a structural model was built using the SWISS-Model server. The interaction between the spike and the human ACE2 was evaluated using two different docking software, Zdock and Haddock. We found that the binding free energy was lower for the Omicron variant as compared to the WT spike. In addition, the Omicron spike protein showed an increased number of electrostatic interactions with ACE2 than the WT spike, especially the interactions related to charged residues. This study contributes to a better understanding of the changes in the interaction between the Omicron spike and the human host ACE2 receptor.

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Section: Resultsmentioning

confidence: 99%

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

2021

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“…From a pool of over 200 human monoclonal antibodies targeting the RBD protein from COVID-19 convalescent samples ( 6 , 26 ), we have identified a linear region recognized by the most potent neutralizing antibody 58G6 ( 27 ). It covers a 20-amino acid (aa) sequence within the receptor-binding motif (RBM) and is named RBD9.1.…”

Section: Resultsmentioning

confidence: 99%

A Highly Conserved Peptide Vaccine Candidate Activates Both Humoral and Cellular Immunity Against SARS-CoV-2 Variant Strains

Gao

Huang

et al. 2021

Front. Immunol.

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Facing the imminent need for vaccine candidates with cross-protection against globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we present a conserved antigenic peptide RBD9.1 with both T-cell and B-cell epitopes. RBD9.1 can be recognized by coronavirus disease 2019 (COVID-19) convalescent serum, particularly for those with high neutralizing potency. Immunization with RBD9.1 can successfully induce the production of the receptor-binding domain (RBD)-specific antibodies in Balb/c mice. Importantly, the immunized sera exhibit sustained neutralizing efficacy against multiple dominant SARS-CoV-2 variant strains, including B.1.617.2 that carries a point mutation (SL452R) within the sequence of RBD9.1. Specifically, SY451 and SY454 are identified as the key amino acids for the binding of the induced RBD-specific antibodies to RBD9.1. Furthermore, we have confirmed that the RBD9.1 antigenic peptide can induce a S448-456 (NYNYLYRLF)-specific CD8+ T-cell response. Both RBD9.1-specific B cells and the S448-456-specific T cells can still be activated more than 3 months post the last immunization. This study provides a potential vaccine candidate that can generate long-term protective efficacy over SARS-CoV-2 variants, with the unique functional mechanism of activating both humoral and cellular immunity.

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“…Antibodies of this IGHV1-58/IGKV3-20 public clonotype bind to the ridge region of SARS-CoV-2 RBD ( Figure 5A ), and can be robustly elicited by infection with antigenically distinct variants of SARS-CoV-2 [39, 47] and by vaccination [48, 49]. These antibodies are also able to potently neutralize multiple variants of concern (VOC) [9, 48, 50]. We compared two previously determined structures of IGHV1-58/IGKV3-20 antibodies in complex with RBD [40, 51], where one has the germline-encoded V L S29 ( Figure 5B ) and the other carries a somatically mutated V L R29 ( Figure 5C ).…”

Section: Resultsmentioning

confidence: 99%

A large-scale systematic survey of SARS-CoV-2 antibodies reveals recurring molecular features

Wang

Yuan

Peng

et al. 2021

Preprint

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In the past two years, the global research in combating COVID-19 pandemic has led to isolation and characterization of numerous human antibodies to the SARS-CoV-2 spike. This enormous collection of antibodies provides an unprecedented opportunity to study the antibody response to a single antigen. From mining information derived from 88 research publications and 13 patents, we have assembled a dataset of ∼8,000 human antibodies to the SARS-CoV-2 spike from >200 donors. Analysis of antibody targeting of different domains of the spike protein reveals a number of common (public) responses to SARS-CoV-2, exemplified via recurring IGHV/IGK(L)V pairs, CDR H3 sequences, IGHD usage, and somatic hypermutation. We further present a proof-of-concept for prediction of antigen specificity using deep learning to differentiate sequences of antibodies to SARS-CoV-2 spike and to influenza hemagglutinin. Overall, this study not only provides an informative resource for antibody and vaccine research, but fundamentally advances our molecular understanding of public antibody responses to a viral pathogen.

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Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Cited by 48 publications

References 45 publications

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

A Highly Conserved Peptide Vaccine Candidate Activates Both Humoral and Cellular Immunity Against SARS-CoV-2 Variant Strains

A large-scale systematic survey of SARS-CoV-2 antibodies reveals recurring molecular features

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