Identification of immunodominant linear epitopes from SARS-CoV-2 patient plasma

Farrera-Soler, Lluc; Daguer, Jean‐Pierre; Barluenga, Sofía; Vadas, Oscar; Cohen, Patrick; Pagano, Sabrina; Yerly, Sabine; Kaiser, Laurent; Vuilleumier, Nicolas; Winssinger, Nicolas

doi:10.1371/journal.pone.0238089

Cited by 85 publications

(109 citation statements)

References 73 publications

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“…Two studies demonstrated a lack of association with affinity [115,145], although a moderate correlation with binding affinity was reported in one study [146]. Potently neutralising N specific antibodies were isolated in other studies [115,148], and the potential for antibodies binding to protease cleavage sites as alternatives to RBD isolated from convalescent plasma has also been identified [153], suggesting an important role in preventing antibody dependent enhancement of viral entry.…”

Section: Protective Immunitymentioning

confidence: 98%

Antibody response to SARS-CoV-2 infection in humans: A systematic review

et al. 2020

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Background Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

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Section: Protective Immunitymentioning

confidence: 98%

Antibody response to SARS-CoV-2 infection in humans: A systematic review

et al. 2020

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“…The targeting of spike proteins by broad-neutralizing antibodies against SARS-CoV-2 offers a potential means of treating and preventing further infections of COVID-19 (Jiang et al, 2020). Evidence on immunodominant epitopes with significantly higher response rates have also been reported (Farrera-Soler et al,2020). Antibody response to SARS-CoV-2 is one of the key immune responses to SARS-CoV-2 which is actively being pursued to develop therapeutic strategies as well as vaccines (Biswas et al, 2020).…”

Section: Introductionmentioning

confidence: 93%

ESC - a comprehensive resource for SARS-CoV-2 immune escape variants

Rophina

Pandhare

Shamnath

et al. 2021

Preprint

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Ever since the breakout of COVID-19 disease, ceaseless genomic research to inspect the epidemiology and evolution of the pathogen has been undertaken globally. Large scale viral genome sequencing and analysis have uncovered the functional impact of numerous genetic variants in disease pathogenesis and transmission. Emerging evidence of mutations in spike protein domains escaping antibody neutralization is reported. We have a precise collation of manually curated variants in SARS-CoV-2 from literature with potential escape mechanisms from a range of neutralizing antibodies. This comprehensive repository encompasses a total of 532 variants accounting for 146 unique variants tested against 75 antibodies and patient convalescent plasma. This resource enables the user to gain access to an extensive annotation of SARS-CoV-2 escape mutations which we hope would contribute to exploring and understanding the underlying mechanisms of immune response against the pathogen. The resource is available at http://clingen.igib.res.in/esc/. Keywords : COVID-19, SARS-CoV-2, Neutralizing antibodies, Escape mutations, Genomes

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“…This might be the case for SARS-CoV-2 when using proteins sharing high homology with genetically similar, co-circulating, human coronaviruses (hCoV) that are responsible for common cold [ 6 , 7 ]. Studies towards fine dissection of the specific regions on the viral proteins recognized by virus-specific antibodies have been recently published focusing on the S protein [ 6 , 8 , 9 , 10 , 11 ]. Moreover, detailed overviews of the epitope landscape within SARS-CoV-2 confirmed interest on the N protein epitopes as valuable markers [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Epitope Mapping on Microarrays Highlights Strong Immune-Response to N Protein Region

et al. 2021

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A workflow for rapid SARS-CoV-2 epitope discovery on peptide microarrays is herein reported. The process started with a proteome-wide screening of immunoreactivity based on the use of a high-density microarray followed by a refinement and validation phase on a restricted panel of probes using microarrays with tailored peptide immobilization through a click-based strategy. Progressively larger, independent cohorts of Covid-19 positive sera were tested in the refinement processes, leading to the identification of immunodominant regions on SARS-CoV-2 spike (S), nucleocapsid (N) protein and Orf1ab polyprotein. A summary study testing 50 serum samples highlighted an epitope of the N protein (region 155–71) providing good diagnostic performance in discriminating Covid-19 positive vs. healthy individuals. Using this epitope, 92% sensitivity and 100% specificity were reached for IgG detection in Covid-19 samples, and no cross-reactivity with common cold coronaviruses was detected. Likewise, IgM immunoreactivity in samples collected within the first month after symptoms onset showed discrimination ability. Overall, epitope 155–171 from N protein represents a promising candidate for further development and rapid implementation in serological tests.

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Identification of immunodominant linear epitopes from SARS-CoV-2 patient plasma

Cited by 85 publications

References 73 publications

Antibody response to SARS-CoV-2 infection in humans: A systematic review

Antibody response to SARS-CoV-2 infection in humans: A systematic review

ESC - a comprehensive resource for SARS-CoV-2 immune escape variants

SARS-CoV-2 Epitope Mapping on Microarrays Highlights Strong Immune-Response to N Protein Region

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