Multiple humans exposed to SARS-CoV-2 elicit an antibody called M15, according to research published in Cell Reports.
The M15 antibody has a rare ability to bind a previously unknown target in the spike protein of the virus by undergoing rare mutations that are highly specific to this antibody class as compared to similar antibodies targeting other pathogens, researchers say.
M15, a public antibody against SAS-CoV-2, undergoes unique mutations in its light chain that are common in different people that elicit this antibody upon infection or vaccination. These mutations help M15 gain access to and bind stronger (increase affinity) to a newly discovered target (or epitope) on the spike protein of SARS-CoV-2. Interestingly, the blood level of antibodies targeting this region increases with multiple vaccine doses.
The findings identify features that differentiate mutations improving the affinity of an antibody and also uncover a novel epitope on the spike protein of SARS-CoV-2.
M15-like antibodies were specifically identified in SARS-CoV-2 infected and vaccinated individuals based on sequence identity. Biolayer interferometry, that measures the affinity of an antibody to its epitope, coupled with a cryo-electron microscopy structure of the M15 molecule in complex with SARS-CoV-2, were used to investigate the role of convergent and clonotype-enriched mutations in improving the affinity of M15. Serum competition ELISA was used to measure the level of antibodies in blood targeting this epitope post infection or vaccination.
Mutations in the light chain that improve affinity of a public antibody, M15, against SARS-CoV-2 are convergently acquired in multiple individuals and are enriched in the public antibody class compared to antibodies recognizing other pathogens. Such mutations help M15 access a highly conserved, novel epitope on the spike protein of SARS-CoV-2. Levels of serum antibodies targeting this viral region increase upon multiple COVID-19 vaccinations.
“Our study shows that certain patterns in antibody mutations, such as clonotype-enrichment and convergence, can help identify which mutations actually make antibodies stronger with respect to binding. This could also be applicable to other diseases, not just COVID-19,” said corresponding author Camila Coelho, PhD, assistant professor of Microbiology, Icahn School of Medicine at Mount Sinai. “It’s a step toward designing smarter vaccines that fine-tune the immune system to produce more potent antibodies.”
Source: Mount Sinai
