Immunologic and biophysical features of the BNT162b2 JN.1 and KP.2 adapted COVID-19 vaccines

Résumé fourni par la source

The rise in prevalence of the SARS-CoV-2 JN.1 lineage in 2023 and subsequent derivative sublineages coincided with reduced neutralizing activity and effectiveness of XBB.1.5-adapted vaccines. Here, we characterize the biophysical and immunologic attributes of BNT162b2 JN.1- and KP.2-adapted mRNA vaccine-encoded spike (S) proteins. We reveal the structural consequences of key amino acid substitutions in S and a potential molecular mechanism of immune escape employed by JN.1 and KP.2 viruses. The two vaccines, administered as fourth or fifth doses in BNT162b2-experienced mice, or as a primary series in naïve mice, confer improved neutralizing responses over the BNT162b2 XBB.1.5-adapted vaccine against a broad panel of JN.1 sublineages. Mapping of neutralizing responses indicate greater antigenic overlap of JN.1 and KP.2 vaccines with JN.1 sublineages, while CD4+ and CD8+ T cell responses are conserved across all three vaccines. These data support the selection of JN.1- or KP.2-adapted vaccines for the 2024-25 COVID-19 vaccine formula. Variation in SARS-CoV-2 viruses results in newly emergent virus lineages. Here, the authors characterize the BNT162b2 mRNA vaccines, adapted to two SARS-CoV-2 lineages, JN.1 and KP.2, measure responses elicited by these vaccines against contemporary and older SARS-CoV-2 variants in naive and antigen experienced animal models and describe the biophysical and structural properties of the spike proteins expressed by these vaccines.

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