Pharma Focus America

Major Advancement: Successful Direct Sequencing of Functional Antibody Proteins from Human Blood

Rapid Novor Inc., a prominent leader in mass spectrometry (MS)-based antibody protein sequencing, has achieved a significant breakthrough. The company's REpAb® antibody discovery platform has successfully sequenced a complex mixture of functional antibodies directly from the serum of a human patient who received a COVID-19 vaccine. This accomplishment represents a remarkable advancement in antibody discovery technology, eliminating the reliance on animal models, DNA, and cells. Xiaobing Han, Principal Scientist for Antibody Discovery at Rapid Novor, highlights the potential of sequencing

functional antibodies generated by the human immune system in response to threats, offering a more direct approach to discovering safe and effective therapeutics.

The study involved using the antigen itself to extract a polyclonal mixture of relevant antibodies from the patient's blood. Through sequencing analysis of the polyclonal population, the researchers identified 12 unique monoclonal antibodies with varying affinities to the antigen, ranging from mid-picomolar to low nanomolar. Notably, seven of these antibodies demonstrated strong affinity and exhibited neutralization capabilities against a pseudovirus in vitro. Remarkably, using a minute volume of human serum, the REpAb® technology provided the necessary protein sequences for generating and reproducing functionally relevant antibodies, surpassing the achievements of previous studies.

To further explore the potential of these antibodies, Rapid Novor combined the REpAb® technology with recombinant expression and cell-based assays. This integration facilitated the decoding of the antibody population from a COVID-19-vaccinated individual. The binding kinetics of the anti-SARS-CoV-2 antibodies were characterized using surface plasmon resonance (SPR) kinetic analysis. Epitope mapping will be conducted using hydrogen-deuterium exchange mass spectrometry (HDX-MS) to gain insights into the antibodies' binding sites. This comprehensive workflow holds promise for driving future innovations in therapeutic antibody research.

Iain Rogers, VP Sales and Marketing at Rapid Novor, underlines the versatility of the REpAb® technology, emphasizing its potential integration into various therapeutic antibody discovery pipelines. With a track record of over 40 successful polyclonal antibody sequencing campaigns, Rapid Novor is actively collaborating with pharmaceutical companies and biotechnology partners to incorporate REpAb® into critical workflows, enabling the discovery of highly potent and developable antibodies.

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