Assessment of SARS-CoV-2 immune escape using antigenic cartography combined with experimental challenge studies.

The disease burden of COVID-19 significantly decreased with the implementation of vaccines. However, SARS-CoV-2 variants that escape vaccine induced immunity continue to emerge and may pose a risk to public health. While vaccine updates are available, it remains uncertain whether they are required for full protection. Here, we antigenically characterized SARS-CoV-2 variants JN.1, KP.2, KP.3.1.1, XEC and LP.8.1 by antigenic cartography and evaluated in vivo protection of JN.1 vaccination in hamsters. Antigenic cartography revealed that these variants are antigenically closely related. In vivo experiments showed that JN.1 vaccination blocked viral replication and inflammation in the lower respiratory tract of JN.1, KP.2 and KP.3.1.1 infected animals. However, despite close antigenic proximity, KP.3.1.1 infected JN.1 vaccinated animals showed evidence of viral replication in the upper respiratory tract, indicative for immune escape. These data demonstrate the strength of combining antigenic cartography with experimental challenge studies to study SARS-CoV-2 immune escape for vaccine updates.