TY - JOUR
T1 - Next-Generation Serology by Mass Spectrometry
T2 - Readout of the SARS-CoV-2 Antibody Repertoire
AU - Melani, Rafael D.
AU - Des Soye, Benjamin J.
AU - Kafader, Jared O.
AU - Forte, Eleonora
AU - Hollas, Michael
AU - Blagojevic, Voislav
AU - Negrão, Fernanda
AU - McGee, John P.
AU - Drown, Bryon
AU - Lloyd-Jones, Cameron
AU - Seckler, Henrique S.
AU - Camarillo, Jeannie M.
AU - Compton, Philip D.
AU - LeDuc, Richard D.
AU - Early, Bryan
AU - Fellers, Ryan T.
AU - Cho, Byoung Kyu
AU - Mattamana, Basil Baby
AU - Goo, Young Ah
AU - Thomas, Paul M.
AU - Ash, Michelle K.
AU - Bhimalli, Pavan P.
AU - Al-Harthi, Lena
AU - Sha, Beverly E.
AU - Schneider, Jeffrey R.
AU - Kelleher, Neil L.
N1 - Funding Information:
RBD was expressed by the Northwestern Recombinant Protein Production Core Facility. The reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Vector pCAGGS Containing the SARS-Related Coronavirus 2, Wuhan-Hu-1 Spike Glycoprotein Receptor-Binding Domain (RBD), NR-52309. IgG glycosylation and bottom-up proteomics were measured by the Northwestern Proteomics Core Facility. This study was funded by the National Institute of Health under a grant from the National Institute of General Medical Sciences P41 GM108569 (N.L.K.); the Research Corporation (Grant no. 27372, N.L.K. and E.F.); Administrative Supplement to SBIR grant number R44 GM121130 (P.D.C.); Walder Foundation grant number SCI16 (J.R.S.); the NIH Office of Director award S10 OD025194 (P.D.C.); the Northwestern Medicine Dr. Michael M. Abecassis Transplant Innovation Endowment Grant; NCI CCSG P30 CA060553 (awarded to the Robert H. Lurie Comprehensive Cancer Center). National Cancer Institute grant 1F32CA246894-01A1 (B.D.); The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2021 American Chemical Society
PY - 2022/1/7
Y1 - 2022/1/7
N2 - 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.
AB - 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.
KW - COVID-19
KW - SARS-CoV-2
KW - antibodies
KW - individual ion mass spectrometry
KW - proteomics
KW - serology
KW - top-down mass spectrometry
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U2 - 10.1021/acs.jproteome.1c00882
DO - 10.1021/acs.jproteome.1c00882
M3 - Article
C2 - 34878788
AN - SCOPUS:85121237927
SN - 1535-3893
VL - 21
SP - 274
EP - 288
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 1
ER -
