A Monoclonal Antibody Panel to Track Ongoing Antigenic Evolution of SARS-CoV-2 Variants

SARS-CoV-2 continues to evolve, generating successive variants with enhanced resistance to antibody-mediated neutralization. However, many existing monoclonal antibody (mAb) repertoires were derived from exposures to ancestral or early Omicron strains and thus incompletely capture the antigenic landscape of newly emerging strains. Here, we generated a mAb panel by immunizing naïve, unimprinted VelocImmune humanized mice with spike from the KP.3.1.1 variant, and isolated and characterized 11 neutralizing antibodies targeting diverse epitopes of recently evolved antigenic variants. We then integrated these antibodies with previously characterized mAbs to establish an expanded toolbox for profiling antigenic evolution among emerging variants. Application of this panel to currently emerging SARS-CoV-2 variants provided mechanistic insight into recent antigenic evolution, highlighting the potential role of altered receptor-binding domain conformation. Our data also revealed clear differences in antibody-evasion profiles between JN.1-derived lineages and BA.3.2 lineages. Together, our findings establish an updated mAb panel for monitoring SARS-CoV-2 antigenic evolution.