Nature Communications (Oct 2024)

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

  • Thierry Le 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,
  • Bin Ma

DOI
https://doi.org/10.1038/s41467-024-53105-8
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

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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.