This study reveals the structural features and immunogenicity of BNT162b2 JN.1 and KP.2 adapted vaccines, showing stronger neutralizing antibody responses against the JN.1 sublineage compared to XBB.1.5 vaccines, providing a scientific basis for updating the 2024-25 vaccine formulations.
Literature Overview
This article, titled 'Immunologic and biophysical features of the BNT162b2 JN.1 and KP.2 adapted COVID-19 vaccines' published in Nature Communications, reviews and summarizes the structural features, key amino acid substitutions, immune escape mechanisms, and the neutralizing antibody and T cell responses elicited in mouse models by the JN.1 and KP.2 SARS-CoV-2 variant vaccines. The study focuses on antigenic drift and the biophysical stability, ACE2 receptor binding enhancement, and antigenic distance from earlier vaccine strains such as XBB.1.5, providing experimental support for the adaptive update of next-generation mRNA vaccines.
Background Knowledge
SARS-CoV-2 continues to evolve, leading to antigenic drift and immune escape, weakening the effectiveness of existing vaccines. JN.1 and KP.2 variants became dominant strains during the winter of 2023–2024, harboring multiple key mutations (e.g., F456L, R346T) in the receptor-binding domain (RBD), which may affect vaccine-induced neutralizing antibody responses. The study employs structural biology and mouse models to systematically analyze conformational changes, receptor binding capacity, and immunogenicity of the spike protein encoded by JN.1 and KP.2 vaccines compared to earlier strains. These analyses are crucial for understanding antigenic drift and optimizing vaccine design. Currently, the global vaccine landscape is transitioning from XBB.1.5 to JN.1/KP.2 adapted vaccines, making immunogenicity assessments of these new strains essential for guiding future vaccine update strategies.
Research Methods and Experiments
Researchers evaluated immune responses in mouse models to JN.1 and KP.2 adapted vaccines compared to the XBB.1.5 vaccine, including neutralizing antibody titers (GMT) and T cell responses. N-linked glycosylation sites of the S protein were analyzed using liquid chromatography-mass spectrometry (LC-MS), while cryo-electron microscopy (cryo-EM) was used to determine conformational changes in the spike protein encoded by JN.1 and KP.2 vaccines. ACE2 binding capacity was also compared. Additionally, cross-reactivity of CD4+ and CD8+ T cell responses was evaluated using peptide pool stimulation assays.
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides structural and immunological evidence supporting the adoption of JN.1 and KP.2 vaccines in the 2024–2025 formulation. Future research should evaluate the real-world efficacy of these vaccines in humans and determine whether cross-protection can be sustained over longer periods, especially against newly emerging antigenically drifted strains. Furthermore, structural and glycosylation analyses of RBD may offer a molecular basis for developing broadly neutralizing antibody vaccines, facilitating the design of more effective pan-Omicron vaccines.
Conclusion
This study systematically analyzed the structural and immunological properties of the BNT162b2 JN.1 and KP.2 adapted vaccines, revealing significantly enhanced neutralizing antibody responses against JN.1 and its sublineages in mouse models, while maintaining broad T cell responses. These findings support the inclusion of JN.1 or KP.2 vaccines in the 2024–2025 formulations to combat the currently dominant viral lineages. The study also highlights how structural changes in the spike protein—including RBD conformational shifts, enhanced ACE2 binding, and acquired glycosylation sites—may influence vaccine performance and relate to immune escape and viral fitness. Future vaccine design should consider both antigenic drift and structural stability to enhance broad protection.
