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

## TL;DR

This study combines antigenic mapping and animal experiments to assess how new SARS-CoV-2 variants escape immunity from vaccines.

## Contribution

The novel contribution is combining antigenic cartography with in vivo challenge studies to evaluate immune escape in SARS-CoV-2 variants.

## Key findings

- SARS-CoV-2 variants JN.1, KP.2, KP.3.1.1, XEC, and LP.8.1 are antigenically similar.
- JN.1 vaccination reduced viral replication and inflammation in the lower respiratory tract of infected hamsters.
- KP.3.1.1 showed signs of immune escape in the upper respiratory tract despite close antigenic similarity to JN.1.

## Abstract

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.