Scientists from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences reported in PLOS Pathogens a series of potent broad-spectrum neutralizing antibodies derived from SARS-CoV-2-infected individuals, along with their neutralization and development mechanisms.

The continuous variation of SARS-CoV-2 poses a significant challenge for vaccine and drug development. Broad-spectrum neutralizing antibodies targeting SARS-CoV-2 and vaccines capable of inducing the production of such antibodies are expected to be effective strategies to counteract viral mutations.

In this study, the team collected blood samples from 11 individuals who had recovered from COVID-19 or received a vaccine. They found that serum from four volunteers had neutralizing activity against all the viral strains tested. Using single B-cell antibody cloning technology, the team isolated 50 monoclonal antibodies that specifically targeted the spike protein of SARS-CoV-2.

Interestingly, the six most potent neutralizing monoclonal antibodies, designated KXD01-06, were derived from the IGHV3-53/3-66 germline gene family. These antibodies demonstrated broad neutralizing activity, including coverage against the original virus strain and newer variants such as EG.5, FL.1.5, and HK.3.

To understand how KXD01-06 achieved its broad-spectrum neutralizing activity, the researchers used deep mutational scanning technology. They discovered that KXD01-06 targets relatively conserved epitopes on the spike protein surface.

In addition, they performed sequence analysis and functional experiments on KXD01-06 and other antibodies from the same gene family, confirming that the degree of antibody affinity maturation plays a critical role in generating broad-spectrum neutralizing activity. This research provides a theoretical basis for the design of novel vaccines based on such broad-spectrum neutralizing antibodies.

"With further design and optimization," said LI Ling, first author of the study, "the monoclonal antibodies KXD01-06 have the potential to be developed into a promising treatment for the prevention of severe COVID-19 infection."