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

  1. Rafael D. Melani
  2. Benjamin J. Des Soye
  3. Jared O. Kafader
  4. Eleonora Forte
  5. Michael Hollas
  6. Voislav Blagojevic
  7. Fernanda Negrão
  8. John P. McGee
  9. Bryon Drown
  10. Cameron Lloyd-Jones
  11. Henrique S. Seckler
  12. Jeannie M. Camarillo
  13. Philip D. Compton
  14. Richard D. LeDuc
  15. Bryan Early
  16. Ryan T. Fellers
  17. Byoung-Kyu Cho
  18. Basil Baby Mattamana
  19. Young Ah Goo
  20. Paul M. Thomas
  21. Michelle K. Ash
  22. Pavan P. Bhimalli
  23. Lena Al-Harthi
  24. Beverly E. Sha
  25. Jeffrey R. Schneider
  26. Neil L. Kelleher
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Abstract

Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present<underline>Ig-MS</underline>, 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 multi-parametric 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 apply Ig-MS to plasma from subjects with severe & mild COVID-19, 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, with compatibility to any recombinant antigen to gauge our immune responses to vaccination, pathogens, or autoimmune disorders.

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