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Virus-like particles (VLPs) have emerged as promising candidates for FMD vaccines but require adjuvants to enhance their immunogenicity. In this study, we evaluated the immunogenicity of a VLP-based vaccine with a water-in-oil-in-water (W\/O\/W) emulsion adjuvant, named WT. Methods: The WT adjuvant was mixed with FMD VLPs to form the VLPs+WT vaccine. The size and stability of the vaccine were analyzed. BALB\/c mice were immunized with the VLPs+WT vaccine, and immunological responses were assessed through antibody measurements, cytokine profiling, and gene expression analysis. In addition, splenic lymphocyte proliferation and signaling pathways were examined. Results: The VLPs+WT vaccine exhibited a homogeneous size of 324.60 \u00b1 2.30 nm and a viscosity of 8.76 mPa\u00b7s, indicating good stability. Immunized mice showed steady weight gain and no organ abnormalities. Compared to the VLPs group, the VLPs+WT group induced significantly higher levels of specific antibodies that persisted for 12 weeks, similar to the commercial VLPs+ISA201 vaccine. The VLPs+WT vaccine also enhanced the secretion of Th1-related (IgG2a, IFN-\u03b3) and Th2-related (IgG1, IL-4) molecules. WT stimulated splenic lymphocyte proliferation and differentiation, primarily activating B-cell receptor signaling and phagosome pathways. It also upregulated genes associated with MHC and interferon stimulation while promoting the expression of MyD88, PI3K, AKT, p65, and p-p65 proteins. Conclusions: These findings suggest that WT is an effective adjuvant for FMD VLP-based vaccines, with potential for improving vaccine efficacy.<\/jats:p>","DOI":"10.3390\/vaccines13010024","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:51:57Z","timestamp":1735631517000},"page":"24","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enhanced Immunogenicity of Foot-and-Mouth Disease Virus-like Particles Using a Water-in-Oil-in-Water Adjuvant"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4519-5823","authenticated-orcid":false,"given":"Yujie","family":"Zhou","sequence":"first","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhu","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhidong","family":"Teng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou 225300, China"},{"name":"Public R&D Platform of Veterinary Vaccines Molecular Design and Formulation Ministry of Agriculture and Rural Affairs, Nanjing 210031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-5010","authenticated-orcid":false,"given":"Yingjuan","family":"Qian","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bihua","family":"Deng","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China"},{"name":"GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou 225300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.vetmic.2016.12.018","article-title":"Foot-and-mouth disease vaccines","volume":"206","author":"Medina","year":"2017","journal-title":"Vet. 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