Peptide microarray‐based analysis of antibody responses to SARS‐CoV‐2 identifies unique epitopes with potential for diagnostic test development

Holenya, Pavlo; Lange, Paul Joris; Reimer, Ulf; Woltersdorf, Wolfram; Panterodt, Thomas; Glas, Michael; Wasner, Mark; Eckey, Maren; Drosch, Michael; Hollidt, Jörg-Michael; Naumann, Michael; Kern, Florian; Wenschuh, Holger; Lange, R; Schnatbaum, Karsten; Bier, Frank F.

doi:10.1002/eji.202049101

Cited by 42 publications

(66 citation statements)

References 39 publications

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“…Thus, we focused on RBD, due to the capacity of RBD protein vaccines to induce strong neutralizing antibody titres [ 21 ]. The poor identification of linear B-cell epitopes using 15-mer peptides [ 38 ], as opposed to results obtained with longer peptides [ 24 , 39 ], forced us to adopt an alternative mapping strategy. In this way we found that half of the tested peptides were immunogenic, and that some of them induced antibodies that recognized the original protein, validating this approach [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses

Aparicio

Casares

Egea

et al. 2021

Emerging Microbes & Infections

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Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund’s adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 10 4 –3 × 10 5 , depending on the adjuvant) and displaying neutralizing capacity (80–95% inhibition capacity; p < 0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes. Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p < 0.01 and p < 0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19.

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Section: Discussionmentioning

confidence: 99%

Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses

Aparicio

Casares

Egea

et al. 2021

Emerging Microbes & Infections

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“…Additionally, recent advances in omics-type approaches present opportunities for in-depth immunological analysis of clinical samples and ex vivo cell cultures, which have not previously been possible due to the remote field location of these trials [117]. Moreover, epitope-mapping techniques can be used with serum collected from vaccinated and putatively immune animals to identify specific natural-and vaccine-induced epitopes displaying a high degree of immunogenicity and associations with protective immunity for further research and development [118,119].…”

Section: Vaccine Trials Against Natural Infection With O Ochengi In Cameroonmentioning

confidence: 99%

Development of a recombinant vaccine against human onchocerciasis

Abraham

Graham-Brown

Carter

et al. 2021

Expert Review of Vaccines

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Introduction: Human onchocerciasis caused by the filarial nematode parasite Onchocerca volvulus remains a major cause of debilitating disease infecting millions primarily in Sub-Saharan Africa. The development of a prophylactic vaccine, along with mass drug administration, would facilitate meeting the goal of onchocerciasis elimination by 2030. Areas covered: Models used to study immunity to Onchocerca include natural infection of cattle with Onchocerca ochengi and O. volvulus infective third-stage larvae implanted within diffusion chambers in mice. A vaccine, comprised of two adjuvanted recombinant antigens, induced protective immunity in genetically diverse mice suggesting that it will function similarly in diverse human populations. These antigens were recognized by immune humans and also induced protective immunity against Brugia malayi. We describe the development of a fusion protein composed of the two vaccine antigens with the plan to test the vaccine in cows and non-human primates as a prelude to the initiation of phase 1 clinical trials. Expert opinion: The adjuvanted O. volvulus vaccine composed of two antigens Ov-103 and Ov-RAL-2 was shown to be consistently effective at inducing protective immunity using multiple immune mechanisms. The vaccine is ready for further evaluation in other animal models before moving to clinical trials in humans.

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“…By combining clinical information, IgG/IgM immune responses and blood parameters, we established a database (COVID-ONE-hi) that provides a one-stop analysis pipeline for COVID-19 specific immune responses and clinical parameters ( Figure 1 B). To help users obtain more COVID-19 serum profiling data, we set up a page on the COVID-ONE-hi website, named “More studies”, to archive other highly related data of COVID-19 serum profiling (protein/peptide microarray/phage display) [ [14] , [15] , [16] , [17] , [18] , [19] ]. In addition, a healthy control dataset was added to the HELP page, which contains the IgG and IgM responses for 528 healthy people against the 21 proteins and spike protein peptides (Table S2).…”

Section: Database Content and Usagementioning

confidence: 99%

COVID-ONE-hi: The One-Stop Database for COVID-19-Specific Humoral Immunity and Clinical Parameters

Xu¹,

Lei

et al. 2021

Genomics, Proteomics &Amp; Bioinformatics

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Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (named COVID-ONE-hi). COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients. In addition, 96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database. Furthermore, COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the “START” button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-hi is freely available at www.COVID-ONE.cn.

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Peptide microarray‐based analysis of antibody responses to SARS‐CoV‐2 identifies unique epitopes with potential for diagnostic test development

Cited by 42 publications

References 39 publications

Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses

Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses

Development of a recombinant vaccine against human onchocerciasis

COVID-ONE-hi: The One-Stop Database for COVID-19-Specific Humoral Immunity and Clinical Parameters

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