Stability of SARS-CoV-2 spike antigens against mutations

ABSTRACT

Modern health care needs preventive vaccines and therapeutic treatments with stability against pathogen mutations to cope with current and future viral infections. At the beginning of the COVID-19 pandemic, our analytic and predictive tool identified a set of eight short SARS-CoV-2 S-spike protein epitopes that had the potential to persistently avoid mutation. Here a combination of genetic, Systems Biology and protein structure analyses confirm the stability of our identified epitopes against viral mutations. Remarkably, this research spans the whole period of the pandemic, during which 93.9% of the eight peptides remained invariable in the globally predominant 43 circulating variants, including Omicron. Likewise, the selected epitopes are conserved in 97% of all 1,514 known SARS-CoV-2 lineages. Finally, experimental analyses performed with these short peptides showed their specific immunoreactivity. This work opens a new perspective on the design of next-generation vaccines and antibody therapies that will remain reliable against future pathogen mutations. HighlightsO_LIOur novel method predicts SARS-CoV-2 epitopes that are stable against future mutations C_LIO_LIGenetic analyses (performed 2 years after epitopes were identified) validate the stability of the identified peptides C_LIO_LIThese epitopes remained invariable in 97% of all 1,514 known SARS-CoV-2 lineages C_LIO_LI93.9% of such peptides were conserved in the 43 variants of most interest, including Omicron C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/22280980v1_ufig1.gif" ALT="Figure 1"> View larger version (45K) org.highwire.dtl.DTLVardef@a9cb10org.highwire.dtl.DTLVardef@152a16corg.highwire.dtl.DTLVardef@1e3cea5org.highwire.dtl.DTLVardef@113ec06_HPS_FORMAT_FIGEXP M_FIG C_FIG