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

Thierry Bihan, Teresa Nunez de Villavicencio Diaz, Chelsea Reitzel, Victoria Lange, Minyoung Park, Emma Beadle, Lin Wu, Marko Jovic, Rosalin M. Dubois, Amber L. Couzens, Jin Duan, Xiaobing Han, Qixin Liu and Bin Ma ()
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Thierry Bihan: Rapid Novor
Teresa Nunez de Villavicencio Diaz: Rapid Novor
Chelsea Reitzel: Rapid Novor
Victoria Lange: Rapid Novor
Minyoung Park: Rapid Novor
Emma Beadle: Rapid Novor
Lin Wu: Rapid Novor
Marko Jovic: Rapid Novor
Rosalin M. Dubois: Rapid Novor
Amber L. Couzens: Rapid Novor
Jin Duan: Rapid Novor
Xiaobing Han: Rapid Novor
Qixin Liu: Rapid Novor
Bin Ma: Rapid Novor

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-53105-8

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