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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月5日

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  • 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,
  • Thomas J. McLellan,
  • Graham M. West,
  • Kristianne P. Dizon,
  • Aaron Yam,
  • Siddartha Mitra,
  • Subrata Saha,
  • Daiana Sharaf,
  • Andrew P. McKeen,
  • Carla I. Cadima,
  • Alexander Muik,
  • Wesley Swanson,
  • Raquel Munoz Moreno,
  • Pilar Mendoza Daroca,
  • Ugur Sahin,
  • Annaliesa S. Anderson,
  • Huixian Wu,
  • Kena A. Swanson,
  • Kayvon Modjarrad

摘要

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.