Breakthrough: Sequencing functional antibody proteins directly from human blood

Reviewed by Megan Craig, M.Sc.Jun 6 2023

Rapid Novor Inc., the world’s leader in mass spectrometry (MS)-based antibody protein sequencing, announced today that its REpAb^® antibody discovery platform was used to successfully sequence a complex mixture of functional antibodies directly from the serum of a human patient after receiving a COVID-19 vaccine.

This demonstrates a significant breakthrough in antibody discovery technology that bypasses the need to work with animal models, DNA, and cells. Sequencing functional antibody molecules produced and selected by the human immune system in response to a threat could mean a much more direct route to discovering safe and effective therapies”.

Xiaobing Han, Principal Scientist for Antibody Discovery, Rapid Novor

The antigen itself was used to extract a polyclonal mixture of relevant antibodies from the blood.

Sequencing analysis of the polyclonal population resulted in the discovery of 12 unique monoclonal antibodies with a range of binding affinities toward the antigen - from mid-picomolar to low nanomolar.”

Thierry Le Bihan, Principal Scientist for pAb sequencing, Rapid Novor

Seven of the antibodies that demonstrated stronger affinity also demonstrated neutralization capabilities  in vitro against a pseudovirus. From a minute human serum sample volume, REpAb^® provided the protein sequences necessary for the generation and reproduction of functionally relevant antibodies - a feat that has yet to be achieved in other studies.

Combining Rapid Novor’s REpAb^® technology with recombinant expression and cell-based assays offered a robust workflow to decode the antibody population of a COVID-19-vaccinated individual. The binding kinetics of these anti-SARS-CoV-2 antibodies were characterized with surface plasmon resonance (SPR) kinetic analysis. Epitope mapping will follow using  hydrogen-deuterium exchange mass spectrometry (HDX-MS). This workflow can potentially provide the information needed for future therapeutic antibody innovations.

The REpAb^® technology is well-positioned to fit into any therapeutic antibody discovery pipeline.”

Iain Rogers, VP Sales and Marketing, Rapid Novor

With 40+ polyclonal antibody sequencing campaigns under their belt, the team at Rapid Novor is actively working with pharmaceutical companies and biotechnology partners to integrate REpAb^® into critical workflows for the discovery of highly potent and developable antibodies.