tetano
Editor, Senior Moderator
Nat Commun
. 2025 Dec 5;16(1):10914.
doi: 10.1038/s41467-025-65896-5. Immunologic and biophysical features of the BNT162b2 JN.1 and KP.2 adapted COVID-19 vaccines
Wei Chen[SUP] #[/SUP][SUP] 1 [/SUP], Kristin R Tompkins[SUP] #[/SUP][SUP] 1 [/SUP], Ian W Windsor[SUP] #[/SUP][SUP] 2 [/SUP], Lyndsey T Martinez[SUP] 1 [/SUP], Minah Ramos[SUP] 1 [/SUP], Weiqiang Li[SUP] 1 [/SUP], Shikha Shrivastava[SUP] 1 [/SUP], Swati Rajput[SUP] 1 [/SUP], Jeanne S Chang[SUP] 2 [/SUP], Parag Sahasrabudhe[SUP] 2 [/SUP], Kimberly F Fennell[SUP] 2 [/SUP], Thomas J McLellan[SUP] 2 [/SUP], Graham M West[SUP] 2 [/SUP], Kristianne P Dizon[SUP] 1 [/SUP], Aaron Yam[SUP] 1 [/SUP], Siddartha Mitra[SUP] 1 [/SUP], Subrata Saha[SUP] 1 [/SUP], Daiana Sharaf[SUP] 1 [/SUP], Andrew P McKeen[SUP] 3 [/SUP], Carla I Cadima[SUP] 4 [/SUP], Alexander Muik[SUP] 4 [/SUP], Wesley Swanson[SUP] 1 [/SUP], Raquel Munoz Moreno[SUP] 1 [/SUP], Pilar Mendoza Daroca[SUP] 1 [/SUP], Ugur Sahin[SUP] 4 [/SUP], Annaliesa S Anderson[SUP] 1 [/SUP], Huixian Wu[SUP] 2 [/SUP], Kena A Swanson[SUP] 5 [/SUP], Kayvon Modjarrad[SUP] 6 [/SUP]
Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
. 2025 Dec 5;16(1):10914.
doi: 10.1038/s41467-025-65896-5. Immunologic and biophysical features of the BNT162b2 JN.1 and KP.2 adapted COVID-19 vaccines
Wei Chen[SUP] #[/SUP][SUP] 1 [/SUP], Kristin R Tompkins[SUP] #[/SUP][SUP] 1 [/SUP], Ian W Windsor[SUP] #[/SUP][SUP] 2 [/SUP], Lyndsey T Martinez[SUP] 1 [/SUP], Minah Ramos[SUP] 1 [/SUP], Weiqiang Li[SUP] 1 [/SUP], Shikha Shrivastava[SUP] 1 [/SUP], Swati Rajput[SUP] 1 [/SUP], Jeanne S Chang[SUP] 2 [/SUP], Parag Sahasrabudhe[SUP] 2 [/SUP], Kimberly F Fennell[SUP] 2 [/SUP], Thomas J McLellan[SUP] 2 [/SUP], Graham M West[SUP] 2 [/SUP], Kristianne P Dizon[SUP] 1 [/SUP], Aaron Yam[SUP] 1 [/SUP], Siddartha Mitra[SUP] 1 [/SUP], Subrata Saha[SUP] 1 [/SUP], Daiana Sharaf[SUP] 1 [/SUP], Andrew P McKeen[SUP] 3 [/SUP], Carla I Cadima[SUP] 4 [/SUP], Alexander Muik[SUP] 4 [/SUP], Wesley Swanson[SUP] 1 [/SUP], Raquel Munoz Moreno[SUP] 1 [/SUP], Pilar Mendoza Daroca[SUP] 1 [/SUP], Ugur Sahin[SUP] 4 [/SUP], Annaliesa S Anderson[SUP] 1 [/SUP], Huixian Wu[SUP] 2 [/SUP], Kena A Swanson[SUP] 5 [/SUP], Kayvon Modjarrad[SUP] 6 [/SUP]
Affiliations
- PMID: 41350251
- PMCID: PMC12680620
- DOI: 10.1038/s41467-025-65896-5
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.