Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire.
Rafael Donadélli MelaniBenjamin J Des SoyeJared O KafaderEleonora ForteMichael A R HollasVoislav BlagojevicFernanda NegrãoJohn P McGeeBryon DrownCameron Lloyd-JonesHenrique Dos Santos SecklerJeannie M CamarilloPhilip D ComptonRichard D LeDucBryan EarlyRyan T FellersByoung-Kyu ChoBasil Baby MattamanaYoung Ah GooPaul M ThomasMichelle K AshPavan P BhimalliLena Al-HarthiBeverly E ShaJeffrey R SchneiderNeil L KelleherPublished in: Journal of proteome research (2021)
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.
Keyphrases
- mass spectrometry
- sars cov
- liquid chromatography
- multiple sclerosis
- respiratory syndrome coronavirus
- high performance liquid chromatography
- capillary electrophoresis
- gas chromatography
- ms ms
- high resolution
- single cell
- binding protein
- endothelial cells
- coronavirus disease
- protein protein
- amino acid
- electronic health record
- single molecule
- artificial intelligence
- big data
- early onset
- inflammatory response
- transcription factor
- machine learning
- dna binding
- pluripotent stem cells
- simultaneous determination
- data analysis
- anaerobic digestion