This paper is now published in Nature Communications!

Le Bihan, T., Nunez de Villavicencio Diaz, T., Reitzel, C. et al. De novo protein sequencing of antibodies for identification of neutralizing antibodies in human plasma post SARS-CoV-2 vaccination. Nat Commun 15, 8790 (2024). https://doi.org/10.1038/s41467-024-53105-8

In this webinar, you will:

  • Explore how using a proteomics approach with REpAb® de novo sequencing accesses a larger diversity of antibodies, and enhances antibody discovery workflows.
  • Case study on de novo sequencing functional and neutralizing antibodies directly from the serum of a Human patient vaccinated against SARS-CoV-2. 
  • Discover novel antibody binders only present in serum that are not found in IgSeq, revealing new candidates for antibody therapeutics.

Antibody Discovery in Humans

The human antibody repertoire is extremely large and diverse, generating as many as 10¹⁸ antibodies in response to foreign pathogens. While B-cell sequencing is an effective method for fully-human antibody discovery, peripheral B cells may not capture the full diversity of circulating antibodies. Circulating B cells only represent 2-3% of total B cells, and not all B cells produce antibodies. This limitation results in overlooked antibodies that are present in serum but missing from B cell sequencing data. For this reason, many antibody discovery scientists are turning to complementary approaches that capture this additional diversity.

Here, we demonstrate a mass spectrometry proteomics-based approach to sequencing functional and neutralizing antibodies directly from the serum of a patient vaccinated against SARS-CoV-2. Following de novo sequencing antibodies from the immunoserum, we recombinantly expressed 12 antibodies. Six derived recombinant antibodies exhibited similar or higher binding affinities than the original natural polyclonal antibody and exhibited neutralizing capabilities.

Additionally, we identified mAb sequences assembled by mass spectrometry based de novo sequencing only, that are not present in IgSeq data, highlighting novel candidates that can only be found in serum. This method is a valuable strategy for interrogating the entire circulating antibody repertoire of animals and humans, enabling the discovery of novel antibody reagents and therapeutics.

Learn more about our antibody discovery services.

Speaker Bios

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