Process parameter optimization and immunogenicity evaluation of calcium phosphate-coated foot-and-mouth disease virus-like particles.

Lihua REN; Wei GUO; Qianqian XIE; Ruipeng LIU; Shiqi SUN; Hu DONG; Yun ZHANG; Manyuan BAI; Huichen GUO; Zhidong TENG

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Process parameter optimization and immunogenicity evaluation of calcium phosphate-coated foot-and-mouth disease virus-like particles.

Author: Lihua REN ¹ ; Wei GUO ¹ ; Qianqian XIE ¹ ; Ruipeng LIU ¹ ; Shiqi SUN ¹ ; Hu DONG ¹ ; Yun ZHANG ¹ ; Manyuan BAI ¹ ; Huichen GUO ¹ ; Zhidong TENG ¹
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1. State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, Gansu, China.
Publication Type:Journal Article
Keywords: calcium phosphate mineralization; foot-and-mouth disease; immunogenicity; reaction conditions; virus-like particles
MeSH: Vaccines, Virus-Like Particle/immunology*; Immunogenicity, Vaccine; Calcium Phosphates/chemistry*; Foot-and-Mouth Disease Virus; Biomineralization; Particle Size; Animals; Mice; Antibodies, Neutralizing/blood*; Antibodies, Viral/blood*; Immunity, Cellular
From: Chinese Journal of Biotechnology 2025;41(7):2672-2681
CountryChina
Language:Chinese
Abstract: Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.