Immunologic and biophysical features of the BNT162b2 JN.1 and KP.2 adapted COVID-19 vaccines
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.
Authors
- Abdoulaye Yam
- Graham M. West (ORCID: https://orcid.org/0000-0003-2157-2123)
- Annaliesa S. Anderson (ORCID: https://orcid.org/0000-0002-6413-1718)
- Kayvon Modjarrad (ORCID: https://orcid.org/0000-0002-6514-5572)
- Thomas J. McLellan
- Kena A. Swanson (ORCID: https://orcid.org/0000-0002-3389-8414)
- Kimberly F. Fennell (ORCID: https://orcid.org/0000-0002-1687-5237)
- Kristin R. Tompkins (ORCID: https://orcid.org/0000-0003-0649-9335)
- Andrew McKeen
- Parag V. Sahasrabudhe (ORCID: https://orcid.org/0000-0002-8442-637X)
- Miguel Ramos (ORCID: https://orcid.org/0000-0003-3648-6818)
- Jeanne S. Chang (ORCID: https://orcid.org/0000-0002-8043-8621)
- Huixian Wu (ORCID: https://orcid.org/0000-0003-1357-9747)
- P. Daroca
- Ian W. Windsor (ORCID: https://orcid.org/0000-0002-6289-6928)
- Swati Rajput (ORCID: https://orcid.org/0000-0003-3708-2014)
- Uğur Şahin (ORCID: https://orcid.org/0000-0003-0363-1564)
- Alexander Muik (ORCID: https://orcid.org/0000-0003-4561-2273)
- Lyndsey T. Martinez (ORCID: https://orcid.org/0009-0009-3967-7776)
- Shikha Shrivastava (ORCID: https://orcid.org/0000-0001-6276-0791)
- William F. Swanson (ORCID: https://orcid.org/0000-0003-4067-0319)
- Carla I. Cadima
- Kristianne P. Dizon
- Weiqiang Li (ORCID: https://orcid.org/0000-0002-8643-359X)
- Wei J. Chen (ORCID: https://orcid.org/0000-0001-5899-5870)
- Subrata Saha (ORCID: https://orcid.org/0000-0002-0146-6166)
- Shweta Mitra
- Raquel Munoz Moreno
- Daiana Sharaf
Institutions
- Pfizer (United States) (US)
- BioNTech (Germany) (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-05
- DOI
- https://doi.org/10.1038/s41467-025-65896-5
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Pfizer