Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire

Melani, Rafael D.; Soye, Benjamin J. Des; Kafader, Jared O.; Forte, Eleonora; Hollas, Michael A.; Blagojevic, Voislav; Negrão, Fernanda; McGee, John P.; Drown, Bryon; Lloyd-Jones, Cameron; Seckler, Henrique S.; Camarillo, Jeannie M.; Compton, Philip D.; LeDuc, Richard D.; Early, Bryan P.; Fellers, Ryan T.; Cho, Byoung-Kyu; Mattamana, Basil Baby; Goo, Young Ah; Thomas, Paul M.; Ash, Michelle K.; Bhimalli, Pavan P.; Al‐Harthi, Lena; Sha, Beverly E.; Schneider, John C.; Kelleher, Neil L.

doi:10.1021/acs.jproteome.1c00882

Cited by 21 publications

(29 citation statements)

References 50 publications

(119 reference statements)

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“…An alternative MS-based method potentially useful for the assessment of IgG Fc glycosylation in COVID-19 is middle-up antibody analysis, as presented for anti-RBD IgG in a study by Melani et al Even though this method is promising, the observed high complexity due to multiple different amino acid sequences and glycan structural heterogeneity complicates Fc glycosylation analysis using this approach [ 34 ].…”

Section: Methods For the Assessment Of Antibody Glycosylation In Covid-19mentioning

confidence: 99%

Antibody glycosylation in COVID-19

2022

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Antibody glycosylation has received considerable attention in coronavirus disease 2019 (COVID-19) infections and recently also in vaccination. Antibody glycosylation and in particular immunoglobulin G1 fucosylation levels influence effector functions and are therefore key parameters for assessing the efficacy and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directed immune responses. This review article summarizes and interprets recent research into antibody glycosylation in COVID-19. Experimental approaches for analyzing the glycosylation of SARS-CoV-2-directed antibody responses are evaluated. The pronounced dynamics, effector functions, clinical utility, and regulation of antibody glycosylation in COVID-19 are assessed. Future research on the role of antibody glycosylation in COVID may cover the glycosylation of other antibody classes beyond immunoglobulin G, the regulation of antibody glycosylation, and the role of non-canonical antibody receptors in determining effector functions. Graphical abstract

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Section: Methods For the Assessment Of Antibody Glycosylation In Covid-19mentioning

confidence: 99%

Antibody glycosylation in COVID-19

2022

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“…Although attempts were made to de novo sequence these antibodies at the intact protein level, the results were limited to a few sequence tags. During the SARS-CoV-2 pandemic, Melani et al 105 focused their profiling efforts on the vaccine-targeted Spike protein receptor-binding domain. The approach is named Ig-MS and features two novel metrics for capturing the intensity and complexity of the antibody response.…”

Section: Protein-centric Sequencing Of Endogenous Antibodiesmentioning

confidence: 99%

A perspective toward mass spectrometry-based de novo sequencing of endogenous antibodies

Graaf

Hoek

Tamara

et al. 2022

mAbs

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A key step in therapeutic and endogenous humoral antibody characterization is identifying the amino acid sequence. So far, this task has been mainly tackled through sequencing of B-cell receptor (BCR) repertoires at the nucleotide level. Mass spectrometry (MS) has emerged as an alternative tool for obtaining sequence information directly at the – most relevant – protein level. Although several MS methods are now well established, analysis of recombinant and endogenous antibodies comes with a specific set of challenges, requiring approaches beyond the conventional proteomics workflows. Here, we review the challenges in MS-based sequencing of both recombinant as well as endogenous humoral antibodies and outline state-of-the-art methods attempting to overcome these obstacles. We highlight recent examples and discuss remaining challenges. We foresee a great future for these approaches making de novo antibody sequencing and discovery by MS-based techniques feasible, even for complex clinical samples from endogenous sources such as serum and other liquid biopsies.

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“…In addition, plasma from 6 vaccinated individuals (3 boosted and 3 not boosted) was collected following infection with Omicron SARS-CoV-2 between December 29, 2021, and January 16, 2022 (Table S1). Plasma preparation was conducted as previously reported . As a standard positive control, we used a commercially obtained plasma sample (CS1) from a convalescent patient infected at the beginning of the pandemic (AllCells).…”

Section: Experimental Sectionmentioning

confidence: 99%

“…The analysis was performed as previously described . Briefly, samples were delivered to the mass spectrometer at a flow rate of 1 μL/min in a fully automated fashion using a a PAL3 robot (CTC Analytics) coupled with a SampleStream flowcell (Integrated Protein Technologies).…”

Section: Experimental Sectionmentioning

confidence: 99%

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Divergent Antibody Repertoires Found for Omicron versus Wuhan SARS-CoV-2 Strains Using Ig-MS

et al. 2022

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SARS-CoV-2 Omicron (B.1.1.529) and its subvariants are currently the most common variants of concern worldwide, featuring numerous mutations in the spike protein and elsewhere that collectively make Omicron variants more transmissible and more resistant to antibody-mediated neutralization provided by vaccination, previous infections, and monoclonal antibody therapies than their predecessors. We recently reported the creation and characterization of Ig-MS, a new mass spectrometry-based serology platform that can define the repertoire of antibodies against an antigen of interest at single proteoform resolution. Here, we applied Ig-MS to investigate the evolution of plasma antibody repertoires against the receptor-binding domain (RBD) of SARS-CoV-2 in response to the booster shot and natural viral infection. We also assessed the capacity for antibody repertoires generated in response to vaccination and/or infection with the Omicron variant to bind to both Wuhan- and Omicron-RBDs. Our results show that (1) the booster increases antibody titers against both Wuhan- and Omicron- RBDs and elicits an Omicron-specific response and (2) vaccination and infection act synergistically in generating anti-RBD antibody repertoires able to bind both Wuhan- and Omicron-RBDs with variant-specific antibodies.

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Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire

Cited by 21 publications

References 50 publications

Antibody glycosylation in COVID-19

Antibody glycosylation in COVID-19

A perspective toward mass spectrometry-based de novo sequencing of endogenous antibodies

Divergent Antibody Repertoires Found for Omicron versus Wuhan SARS-CoV-2 Strains Using Ig-MS

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