ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Veterinary and Zoonotic Infection
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1676592
This article is part of the Research TopicUnveiling Host-Pathogen Interactions: Insights into Animal Cellular Immunity and Novel Diagnostics - Volume IIView all 21 articles
Ferritin nanoparticle vaccine displaying optimized Spike protein confers broad protection against Omicron subvariants
Provisionally accepted
- 1Jilin Medical University, Jilin, China
- 2Chinese Academy of Agricultural Sciences Changchun Veterinary Research Institute, Changchun, China
- 3Wenzhou University, Wenzhou, China
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Introduction: The newly emerged Omicron subvariants demonstrate resistance to current therapeutic antibodies and an enhanced ability to evade the vaccine-induced immune responses. Among them, JN.1 sub-lineages are considered highly immune-evasive, underscoring the urgent need for broadly protective vaccines. Ferritin nanoparticles, with their unique hollow nanocage structure, provide an efficient antigen-display platform for next-generation vaccine development. Methods: Based on the previously constructed Delta-6P-S recombinant protein vaccine with broad-spectrum protective effects, this study optimized the S protein structure displayed on the surface of ferritin nanoparticles by comparing the immune responses induced in C57BL/6J mice. Results: Delta-4S1158 nanoparticles, containing a truncated S-6P structure with four additional mutation sites, elicited robust S-specific IgG, potent neutralizing antibodies, and a Th2-biased T cell response in C57BL/6J mice, demonstrating favorable immunogenicity and safety. The JN.1-4S1158 nanoparticles, based on this structural design, induced a strong cross-neutralizing antibody response in C57BL/6J mice and conferred effective protection against Omicron BA.5, XBB, and JN.1 variants. Vaccinated mice exhibited significantly reduced viral genomic loads in trachea and lung tissues compared to controls, with no infectious virus detected. Lung tissue pathology was minimal in vaccinated mice. Conclusion: JN.1-4S1158 nanoparticle vaccine demonstrates broad-spectrum protective effects against Omicron subvariants and shows potential for further development. It also provides a basis for the development of a universal SARS-CoV-2 vaccine.
Keywords: immune-evasive, Ferritin nanoparticles, Immunogenicity, Cross-neutralizing, omicron
Received: 30 Jul 2025; Accepted: 17 Oct 2025.
Copyright: © 2025 Feng, Yu, Wang, Li, Li, Wang, Ha and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sheng Feng, fengsheng19940504@163.com
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