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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 # 1 , Kristin R Tompkins # 1 , Ian W Windsor # 2 , Lyndsey T Martinez 1 , Minah Ramos 1 , Weiqiang Li 1 , Shikha Shrivastava 1 , Swati Rajput 1 , Jeanne S Chang 2 , Parag Sahasrabudhe 2 , Kimberly F Fennell 2 , Thomas J McLellan 2 , Graham M West 2 , Kristianne P Dizon 1 , Aaron Yam 1 , Siddartha Mitra 1 , Subrata Saha 1 , Daiana Sharaf 1 , Andrew P McKeen 3 , Carla I Cadima 4 , Alexander Muik 4 , Wesley Swanson 1 , Raquel Munoz Moreno 1 , Pilar Mendoza Daroca 1 , Ugur Sahin 4 , Annaliesa S Anderson 1 , Huixian Wu 2 , Kena A Swanson 5 , Kayvon Modjarrad 6
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+ 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.
. 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 # 1 , Kristin R Tompkins # 1 , Ian W Windsor # 2 , Lyndsey T Martinez 1 , Minah Ramos 1 , Weiqiang Li 1 , Shikha Shrivastava 1 , Swati Rajput 1 , Jeanne S Chang 2 , Parag Sahasrabudhe 2 , Kimberly F Fennell 2 , Thomas J McLellan 2 , Graham M West 2 , Kristianne P Dizon 1 , Aaron Yam 1 , Siddartha Mitra 1 , Subrata Saha 1 , Daiana Sharaf 1 , Andrew P McKeen 3 , Carla I Cadima 4 , Alexander Muik 4 , Wesley Swanson 1 , Raquel Munoz Moreno 1 , Pilar Mendoza Daroca 1 , Ugur Sahin 4 , Annaliesa S Anderson 1 , Huixian Wu 2 , Kena A Swanson 5 , Kayvon Modjarrad 6
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+ 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.