Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

Chen, Elaine C.; Gilchuk, Pavlo; Zost, Seth J.; Suryadevara, Naveenchandra; Winkler, Emma S.; Cabel, Carly R.; Binshtein, Elad; Chen, Rita E.; Sutton, Rachel E.; Rodríguez, Jessica; Day, Samuel B.; Myers, Luke; Trivette, Andrew; Williams, Jazmean K.; Davidson, Edgar; Li, Shuaizhi; Doranz, Benjamin J.; Campos, Samuel K.; Carnahan, Robert H.; Thorne, Curtis A.; Diamond, Michael S.

doi:10.1016/j.celrep.2021.109604

Cited by 83 publications

(98 citation statements)

References 89 publications

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“…Most recently, it has been reported that the combination of COV2-2130 and COV2-2196 can neutralize SARS-CoV-2 variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1429 (Epsilon), B.1617.1, or B.1526 (Iota), in vitro. From the analysis of prophylactic and therapeutic efficacies against B.1.1.7 (Alpha), B.1.351 (Beta), or P.1 (Gamma) in animals, AZD7442 showed promising results [ 105 ]. In November 2021, new data from two phase III trials testing AZD7442 for prophylaxis and post-exposure prophylaxis were released (Table 2 ).…”

Section: Therapeutic Absmentioning

confidence: 99%

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

et al. 2022

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The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity and reliability, monoclonal antibodies (mAbs) have emerged as powerful tools to treat and detect numerous diseases. Hence, many researchers have begun to urgently develop Ab-based kits for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ab drugs for use as COVID-19 therapeutic agents. The detailed structure of the SARS-CoV-2 spike protein is known, and since this protein is key for viral infection, its receptor-binding domain (RBD) has become a major target for therapeutic Ab development. Because SARS-CoV-2 is an RNA virus with a high mutation rate, especially under the selective pressure of aggressively deployed prophylactic vaccines and neutralizing Abs, the use of Ab cocktails is expected to be an important strategy for effective COVID-19 treatment. Moreover, SARS-CoV-2 infection may stimulate an overactive immune response, resulting in a cytokine storm that drives severe disease progression. Abs to combat cytokine storms have also been under intense development as treatments for COVID-19. In addition to their use as drugs, Abs are currently being utilized in SARS-CoV-2 detection tests, including antigen and immunoglobulin tests. Such Ab-based detection tests are crucial surveillance tools that can be used to prevent the spread of COVID-19. Herein, we highlight some key points regarding mAb-based detection tests and treatments for the COVID-19 pandemic.

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Section: Therapeutic Absmentioning

confidence: 99%

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

et al. 2022

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“…However, it must be recognized that the use of mAbs for longterm treatment or prevention, especially in chronic infected individuals who are immunocompromised, may lead to the emergence of neutralization resistance mutations. In order to avoid selective pressure and immune escape, it is suggested that antibody therapy might consist of a combination of antibodies targeting non-overlapping or highly conserved epitopes (129). Considering the important role of site 484 for antibody binding and neutralization, it is a good strategy to identify monoclonal antibodies from E484K infected individuals (59).…”

Section: Discussionmentioning

confidence: 99%

Understanding the Secret of SARS-CoV-2 Variants of Concern/Interest and Immune Escape

Lou

Pang

et al. 2021

Front. Immunol.

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The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global public health. Four SARS-CoV-2 variants of concern including B.1.1.7, B.1.351, B.1.617.2, and P.1, and two variants of interest including C.37 and B.1.621 have been reported to have potential immune escape, and one or more mutations endow them with worrisome epidemiologic, immunologic, or pathogenic characteristics. This review introduces the latest research progress on SARS-CoV-2 variants of interest and concern, key mutation sites, and their effects on virus infectivity, mortality, and immune escape. Moreover, we compared the effects of various clinical SARS-CoV-2 vaccines and convalescent sera on epidemic variants, and evaluated the neutralizing capability of several antibodies on epidemic variants. In the end, SARS-CoV-2 evolution strategies in different transmission stages, the impact of different vaccination strategies on SARS-CoV-2 immune escape, antibody therapy strategies and COVID-19 epidemic control prospects are discussed. This review will provide a systematic and comprehensive understanding of the secret of SARS-CoV-2 variants of interest/concern and immune escape.

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“…The public antibody response to SARS-CoV-2 has also been examined by a recent data mining study that focused on identifying public clonotypes [55]. This previous study defined public clonotypes as antibodies with the same IGHV/IGHJ/IGK(L)V/IGK(L)V genes and high similarity of CDR H3 [55]. While multiple public clonotypes were identified using this stringent definition [55], the characterization of public antibody response is likely far from comprehensive.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…This previous study defined public clonotypes as antibodies with the same IGHV/IGHJ/IGK(L)V/IGK(L)V genes and high similarity of CDR H3 [55]. While multiple public clonotypes were identified using this stringent definition [55], the characterization of public antibody response is likely far from comprehensive. A public antibody response may not always involve a defined pair of IGHV/IGK(L)V genes, especially when either IGHV or IGK(L)V gene-encoded residues only make a minimal contribution to the paratope.…”

Section: Discussionmentioning

confidence: 99%

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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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Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

Cited by 83 publications

References 89 publications

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Understanding the Secret of SARS-CoV-2 Variants of Concern/Interest and Immune Escape

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

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