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

Author

Listed:
  • Wei Chen

    (Pfizer Vaccines)

  • Kristin R. Tompkins

    (Pfizer Vaccines)

  • Ian W. Windsor

    (Pfizer Discovery Sciences)

  • Lyndsey T. Martinez

    (Pfizer Vaccines)

  • Minah Ramos

    (Pfizer Vaccines)

  • Weiqiang Li

    (Pfizer Vaccines)

  • Shikha Shrivastava

    (Pfizer Vaccines)

  • Swati Rajput

    (Pfizer Vaccines)

  • Jeanne S. Chang

    (Pfizer Discovery Sciences)

  • Parag Sahasrabudhe

    (Pfizer Discovery Sciences)

  • Kimberly F. Fennell

    (Pfizer Discovery Sciences)

  • Thomas J. McLellan

    (Pfizer Discovery Sciences)

  • Graham M. West

    (Pfizer Discovery Sciences)

  • Kristianne P. Dizon

    (Pfizer Vaccines)

  • Aaron Yam

    (Pfizer Vaccines)

  • Siddartha Mitra

    (Pfizer Vaccines)

  • Subrata Saha

    (Pfizer Vaccines)

  • Daiana Sharaf

    (Pfizer Vaccines)

  • Andrew P. McKeen

    (Pfizer Data Sciences and Analytics)

  • Carla I. Cadima

    (BioNTech)

  • Alexander Muik

    (BioNTech)

  • Wesley Swanson

    (Pfizer Vaccines)

  • Raquel Munoz Moreno

    (Pfizer Vaccines)

  • Pilar Mendoza Daroca

    (Pfizer Vaccines)

  • Ugur Sahin

    (BioNTech)

  • Annaliesa S. Anderson

    (Pfizer Vaccines)

  • Huixian Wu

    (Pfizer Discovery Sciences)

  • Kena A. Swanson

    (Pfizer Vaccines)

  • Kayvon Modjarrad

    (Pfizer Vaccines)

Abstract

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.

Suggested Citation

  • Wei Chen & Kristin R. Tompkins & Ian W. Windsor & Lyndsey T. Martinez & Minah Ramos & Weiqiang Li & Shikha Shrivastava & Swati Rajput & Jeanne S. Chang & Parag Sahasrabudhe & Kimberly F. Fennell & Tho, 2025. "Immunologic and biophysical features of the BNT162b2 JN.1 and KP.2 adapted COVID-19 vaccines," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65896-5
    DOI: 10.1038/s41467-025-65896-5
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