Scientists from Hefei Institutes of Physical Science (HFIPS) of Chinese Academy of Sciences (CAS) reported a series of potent broad-spectrum neutralizing antibodies derived from individuals infected with SARS-CoV-2, along with their mechanisms of neutralization and development in PLOS Pathogens recently.
The continuous variation of SARS-CoV-2 poses a significant challenge to 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 in addressing viral mutations.
In this research, the team collected blood samples from 11 individuals who had recovered from COVID-19 or received a vaccine. They found that four volunteers' serum exhibited neutralizing activity against all tested viral strains. Using single B cell cloning antibody technology, the team isolated 50 monoclonal antibodies that specifically targeted the spike protein of SARS-CoV-2.
Interestingly, the six most powerful neutralizing monoclonal antibodies, named KXD01-06, were derived from the IGHV3-53/3-66 germline gene family. These antibodies demonstrated broad-spectrum 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 targeted relatively conserved epitopes on the spike protein surface. Furthermore, 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 crucial 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 paper, "the monoclonal antibodies KXD01-06 have the potential to be developed into a promising treatment for preventing severe COVID-19 infection."
The degree of antibody affinity maturation is a critical factor for the generation of broad-spectrum neutralizing activity. (Image by LI Ling)