De novo protein sequencing of antibodies for identification of neutralizing antibodies in human plasma post SARS-CoV-2 vaccination.

De novo protein sequencing of antibodies for identification of neutralizing antibodies in human plasma post SARS-CoV-2 vaccination.

Publication date: Oct 10, 2024

The antibody response to vaccination and infection is a key component of the immune response to pathogens. Sequencing of peripheral B cells may not represent the complete B cell receptor repertoire. Here we present a method for sequencing human plasma-derived polyclonal IgG using a combination of mass spectrometry and B-cell sequencing. We investigate the IgG response to the Moderna Spikevax COVID-19 vaccine. From the sequencing data of the natural polyclonal response to vaccination, we generate 12 recombinant antibodies. Six derived recombinant antibodies, including four generated with de novo protein sequencing, exhibit similar or higher binding affinities than the original natural polyclonal antibody. Neutralization tests reveal that the six antibodies possess neutralizing capabilities against the target antigen. This research provides insights into sequencing polyclonal IgG antibodies and the potential of our approach in generating recombinant antibodies with robust binding affinity and neutralization capabilities. Directly examining the circulating IgG pool is crucial due to potential misrepresentations by B-cell analysis alone.

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Concepts Keywords
Antibodies Antibodies, Neutralizing
Covid Antibodies, Neutralizing
Moderna Antibodies, Viral
Pool Antibodies, Viral
Spectrometry B-Lymphocytes
COVID-19
COVID-19 Vaccines
COVID-19 Vaccines
Humans
Immunoglobulin G
Immunoglobulin G
Neutralization Tests
Recombinant Proteins
Recombinant Proteins
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Vaccination

Semantics

Type Source Name
disease IDO protein
disease MESH infection
disease IDO immune response
disease IDO cell
drug DRUGBANK Amber
disease MESH cancer
drug DRUGBANK Adalimumab
drug DRUGBANK Coenzyme M
drug DRUGBANK Daratumumab
drug DRUGBANK Ustekinumab
disease IDO blood
disease MESH COVID 19
drug DRUGBANK L-Isoleucine
drug DRUGBANK L-Leucine
drug DRUGBANK Immune Globulin Human
drug DRUGBANK Biotin
disease IDO production
drug DRUGBANK Trypsin
drug DRUGBANK Chymotrypsin
drug DRUGBANK Pepsin
drug DRUGBANK Sulfacetamide
drug DRUGBANK L-Cysteine
drug DRUGBANK L-Lysine
disease IDO assay
disease IDO process
pathway REACTOME Digestion
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK L-Arginine
drug DRUGBANK Ilex paraguariensis leaf
disease MESH dissociation
drug DRUGBANK Bevacizumab
drug DRUGBANK Cetuximab
drug DRUGBANK Cefalotin
drug DRUGBANK Rituximab
drug DRUGBANK Trastuzumab
disease IDO humoral immune response
drug DRUGBANK L-Valine
drug DRUGBANK Spinosad
disease IDO reagent
drug DRUGBANK Aspartame
drug DRUGBANK Ethanol
drug DRUGBANK Water
drug DRUGBANK Phosphate ion
drug DRUGBANK Glycine
drug DRUGBANK Indoleacetic acid
drug DRUGBANK Urea
drug DRUGBANK Tromethamine
drug DRUGBANK Iron
drug DRUGBANK Formic Acid
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Monofluorophosphate ion
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Sodium carbonate
drug DRUGBANK Edetic Acid
pathway REACTOME Translation
disease IDO algorithm
drug DRUGBANK Amino acids
drug DRUGBANK Glutamic Acid
drug DRUGBANK Trifluoro-thiamin phosphate
disease MESH pemphigus
disease MESH hodgkin’s disease
pathway REACTOME Reproduction

Original Article

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