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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.

Original languageEnglish (US)
Pages (from-to)274-288
Number of pages15
JournalJournal of Proteome Research
Issue number1
StatePublished - Jan 7 2022


  • COVID-19
  • SARS-CoV-2
  • antibodies
  • individual ion mass spectrometry
  • proteomics
  • serology
  • top-down mass spectrometry

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry


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