Thangsunan Patcharapong, Thangsunan Pattanapong, Mahatnirunkul Thanisorn, Buncharoen Wararut, Saenphet Kanokporn, Saenphet Supap, Phaksopa Jitraporn, Thompson Kim D, Srisapoome Prapansak, Kumwan Benchawan, Meachasompop Pakapon, Suree Nuttee, Uchuwittayakul Anurak
Office of Research Administration, Chiang Mai University, Chiang Mai, 50200, Thailand; Division of Biochemistry and Biochemical Innovation, Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand.
Division of Biochemistry and Biochemical Innovation, Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence for Innovation in Chemistry, And Research Laboratory on Advanced Materials for Sensor and Biosensor Innovation, Material Science Research Center, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand.
Fish Shellfish Immunol. 2025 Oct;165:110483. doi: 10.1016/j.fsi.2025.110483. Epub 2025 Jun 10.
Traditional oral vaccines often face several challenges, such as antigen degradation and poor immune activation due to harsh gastrointestinal conditions. To address this, an effective oral vaccine was developed using hydrogel beads made of sodium alginate (SA), calcium bentonite (BN), and chitosan (CS) to generate microspheres that can encapsulate F. oreochromis (Fo) cells as an oral vaccine (SA/BN/CS hydrogel Fo-OV) for hybrid red tilapia. This study demonstrates that oral administration of a Fo-encapsulated hydrogel bead vaccine (Fo-OV hydrogel) can effectively protect the antigen from gastric degradation and release it to fish intestine, as indicated by in vitro studies showing color and structural changes under different pH conditions, allowing the controlled antigen release. This led to significant enhancements in both systemically and predominantly mucosal immune responses in hybrid red tilapia (Oreochromis spp.) after 14 and 28 days post consecutive 7-day vaccination. The vaccine increased the specific IgM antibody to F. oreochromis in serum and mucosal tissues, and increased the expression of immunoglobulin repertoire genes, IgM, IgT, and IgD in mucosal tissues, indicating activation of the fish immune system. Histological examinations revealed the beneficial changes in the intestinal mucosa by increasing the thickness of lamina propria and causing an increasing number of Goblet cells without any pathological abnormalities in the liver or intestines. Moreover, the Fo-OV hydrogel group showed significantly higher survival rates after the challenge with F. oreochromis than control groups and traditional formalin-killed Fo vaccine. These findings suggest that the hydrogel formulation can protect the antigen from degradation and enhance their uptake by mucosal-associated lymphoid tissues (MALTs), leading to stronger and more specific immune responses. The outcome of this research could be an invaluable tool as the potential application of hydrogel-based vaccines in aquaculture to improve fish health and disease resistance.
传统口服疫苗常常面临诸多挑战，比如抗原降解以及由于恶劣的胃肠道环境导致的免疫激活不佳。为解决这一问题，利用由海藻酸钠（SA）、钙基膨润土（BN）和壳聚糖（CS）制成的水凝胶珠来开发一种有效的口服疫苗，以生成可将奥利亚罗非鱼（Fo）细胞封装为杂交红罗非鱼口服疫苗（SA/BN/CS水凝胶Fo-OV）的微球。本研究表明，口服封装有Fo的水凝胶珠疫苗（Fo-OV水凝胶）可有效保护抗原免受胃部降解，并将其释放到鱼肠道中，体外研究显示在不同pH条件下颜色和结构变化，这表明可实现可控的抗原释放。在连续7天接种疫苗后的14天和28天，这使得杂交红罗非鱼（奥利亚罗非鱼属）的全身和主要黏膜免疫反应均得到显著增强。该疫苗增加了血清和黏膜组织中针对奥利亚罗非鱼的特异性IgM抗体，并增加了黏膜组织中免疫球蛋白库基因IgM、IgT和IgD的表达，表明鱼免疫系统被激活。组织学检查显示，通过增加固有层厚度并使杯状细胞数量增加，肠道黏膜发生了有益变化，而肝脏或肠道未出现任何病理异常。此外，在用奥利亚罗非鱼进行攻毒后，Fo-OV水凝胶组的存活率显著高于对照组和传统福尔马林灭活的Fo疫苗。这些发现表明，水凝胶制剂可保护抗原不被降解，并增强黏膜相关淋巴组织（MALT）对其的摄取，从而引发更强且更具特异性的免疫反应。这项研究的成果可能成为一种极具价值的工具，因为基于水凝胶的疫苗在水产养殖中具有改善鱼类健康和抗病能力的潜在应用价值。
