Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein

Poh, Chek Meng; Carissimo, Guillaume; Wang, Bei; Amrun, Siti Naqiah; Lee, Cheryl Yi‐Pin; Chee, Rhonda Sin‐Ling; Yeo, Nicholas Kim‐Wah; Lee, Wen-Hsin; Leo, Yee‐Sin; Chen, Mark; Tan, Seow‐Yen; Chai, Louis Yi Ann; Kalimuddin, Shirin; Thien, S L; Young, Barnaby Edward; Lye, David C.; Wang, Cheng‐I; Rénia, Laurent; Ng, Lisa F. P.

doi:10.1101/2020.03.30.015461

Cited by 27 publications

(44 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 Surprisingly, the prediction revealed no B-cell epitope within the RBD of the S protein; however, several candidate epitopes were identified outside the RBD and within S2 (Figure 1). The predictions are corroborated by the identification of two immunodominant linear B-cell epitopes that are highly recognized by neutralizing antibodies in sera of COVID-19 convalescent patients 8 (Figure 1, yellow squares). Importantly, some of the predicted identified epitopes show a high degree of conservation between SARS-CoV and SARS-CoV-2.…”

Section: Sars-cov-2 Immunogenicity At the Crossroadsmentioning

confidence: 61%

SARS‐CoV‐2 immunogenicity at the crossroads

Karamloo

König

2020

Allergy

View full text Add to dashboard Cite

Section: Sars-cov-2 Immunogenicity At the Crossroadsmentioning

confidence: 61%

SARS‐CoV‐2 immunogenicity at the crossroads

Karamloo

König

2020

Allergy

View full text Add to dashboard Cite

“…Note that epitopes 12426 and 558417 share the same sequence; they have different IDs due to differences in the associated experimental procedures. The epitopes with IEDB IDs 52020 and 16183 overlap with the regions reported to be recognized by neutralizing antibodies in the sera of recovered COVID-19 patients 8 . 9,10 .…”

Section: Figure 2 B Cell Linear Epitopes In the Spike Protein Of Sarmentioning

confidence: 80%

“…Conversely, studies have demonstrated that specific SARS-CoV-derived antibodies binding to the spike's receptor binding domain, which has significant genetic differences in SARS-CoV-2, have limited cross-reactivity 7 . Antibody and T cell responses against spike protein epitopes that are genetically similar in SARS-CoV and SARS-CoV-2 have also been reported in COVID-19 infected patients [8][9][10] , and in preclinical vaccine trials 11,12 . Epitopes recommended by COVIDep have notable overlap with the findings in these experimental studies (Figures 2 and 3).…”

Section: Descriptionmentioning

confidence: 85%

COVIDep platform for real-time reporting of vaccine target recommendations for SARS-CoV-2: Description and connections with COVID-19 immune responses and preclinical vaccine trials

Ahmed

Quadeer

McKay

2020

Preprint

View full text Add to dashboard Cite

We introduce COVIDep (https://COVIDep.ust.hk), a web-based platform that provides immune target recommendations for guiding SARS-CoV-2 vaccine development. COVIDep implements a protocol that pools together publicly-available genetic data for SARS-CoV-2 and epitope data for SARS-CoV to identify B cell and T cell epitopes that present potential immune targets for SARS-CoV-2. Correspondences between outputs of COVIDep and immune responses recorded in COVID-19 patients and preclinical vaccine trials are also indicated. The platform is user-friendly, flexible, and based on up-to-date data. It may help guide vaccine designs and associated experimental studies for SARS-CoV-2.

show abstract

“…In addition to identifying SARS-CoV-2 T cell epitopes, we sought to identify a set of linear B cell epitopes on the Spike protein which would serve as good targets for stimulating neutralizing antibody responses ( Figure 1 ). Epitope candidates were derived from four published preprint mapping/array studies [56][57][58][59] and one as-of-yet unpublished PEPperCHIP ® peptide array study (for study details see Methods: Antibody epitope curation ). Starting with an initial candidate pool of 58 linear epitopes with data to support in vivo generation in humans ( Figure 4A, Table S4 ), we applied a set of filtering criteria to narrow our target space ( Figure 4B ):…”

Section: B Cell Epitope Predictionmentioning

confidence: 99%

Landscape and Selection of Vaccine Epitopes in SARS-CoV-2

Smith

Entwistle

Willis

et al. 2020

Preprint

View full text Add to dashboard Cite

There is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized for concurrent B cell, CD4 + T cell, and CD8 + T cell stimulation would drive both humoral and cellular immunity with high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE). Additionally, such vaccines can be rapidly manufactured in a distributed manner. In this study, we combine computational prediction of T cell epitopes, recently published B cell epitope mapping studies, and epitope accessibility to select candidate peptide vaccines for SARS-CoV-2. We begin with an exploration of the space of possible T cell epitopes in SARS-CoV-2 with interrogation of predicted HLA-I and HLA-II ligands, overlap between predicted ligands, protein source, as well as concurrent human/murine coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, viral source protein abundance, sequence conservation, coverage of high frequency HLA alleles and co-localization of CD4 + and CD8 + T cell epitopes. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering to select regions with surface accessibility, high sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. From 58 initial candidates, three B cell epitope regions were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we propose a set of SARS-CoV-2 vaccine peptides for use in subsequent murine studies and clinical trials. Figure 2: Landscape of SARS-CoV-2 MHC ligands. (A&B) Selection criteria for (A) HLA-I and (B) shows predicted (x-axis) versus IEDB (y-axis) binding affinity, with horizontal line representing 500nM IEDB binding affinity and vertical line representing corresponding predicted binding affinity for 90% specificity in binding prediction. Histogram (top) shows all predicted SARS-CoV-2 HLA ligand candidates. (C) Landscape of predicted HLA ligands, showing nested HLA ligands comprising HLA-I and -II ligands with complete overlap (top), and LOESS fitted curve (span = 0.1) for HLA-I/II ligands by location along the . Red track represents SARS epitopes identified in literature review with sequence identity in SARS-CoV-2. Predicted HLA ligands with conserved sequences to this literature set are represented in the lollipop plot with a red stick. (D) Summary of total number of predicted HLA-I/II ligands and nested HLA ligands. (E) Summary of nested HLA ligand coverage by protein, with raw counts (left) or counts normalized by protein length (right). (F) Summary of murine/human MHC ligand overlap. (G) Distribution of population frequencies among predicted HLA-I, -II, and nested HLA ligands.

show abstract

Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein

Abstract: words) 46The ongoing SARS-CoV-2 pandemic demands rapid identification of immunogenic 47

Cited by 27 publications

References 14 publications

SARS‐CoV‐2 immunogenicity at the crossroads

SARS‐CoV‐2 immunogenicity at the crossroads

COVIDep platform for real-time reporting of vaccine target recommendations for SARS-CoV-2: Description and connections with COVID-19 immune responses and preclinical vaccine trials

Landscape and Selection of Vaccine Epitopes in SARS-CoV-2

Contact Info

Product

Resources

About