Ju Ruibao, Lu Yanjing, Jiang Zhiwen, Chi Jinhua, Wang Shuo, Liu Wanshun, Yin Yanbo, Han Baoqin
Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.
College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China.
Polymers (Basel). 2024 Oct 4;16(19):2815. doi: 10.3390/polym16192815.
Brucellosis is a zoonotic infectious disease that has long endangered the development of animal husbandry and human health. Currently, vaccination stands as the most efficacious method for preventing and managing brucellosis. Alum, as the most commonly used adjuvant for the brucellosis vaccine, has obvious disadvantages, such as the formation of granulomas and its non-degradability. Therefore, the aims of this study were to prepare an absorbable, injectable, and biocompatible hydroxypropyl chitin (HPCT) thermosensitive hydrogel and to evaluate its immunization efficacy as an adjuvant for Brucella antigens. Specifically, etherification modification of marine natural polysaccharide chitin was carried out to obtain a hydroxypropyl chitin. Rheological studies demonstrated the reversible temperature sensitivity of HPCT hydrogel. Notably, 5 mg/mL of bovine serum albumin can be loaded in HPCT hydrogels and released continuously for more than one week. Furthermore, the L929 cytotoxicity test and in vivo degradation test in rats proved that an HPCT hydrogel had good cytocompatibility and histocompatibility and can be degraded and absorbed in vivo. In mouse functional experiments, as adjuvants for Brucella antigens, an HPCT hydrogel showed better specific antibody expression levels and cytokine (Interleukin-4, Interferon-γ) expression levels than alum. Thus, we believe that HPCT hydrogels hold much promise in the development of adjuvants.
布鲁氏菌病是一种人畜共患传染病，长期以来危及畜牧业发展和人类健康。目前，疫苗接种是预防和控制布鲁氏菌病最有效的方法。明矾作为布鲁氏菌病疫苗最常用的佐剂，存在明显缺点，如形成肉芽肿且不可降解。因此，本研究的目的是制备一种可吸收、可注射且具有生物相容性的羟丙基甲壳素（HPCT）热敏水凝胶，并评估其作为布鲁氏菌抗原佐剂的免疫效果。具体而言，对海洋天然多糖甲壳素进行醚化改性以获得羟丙基甲壳素。流变学研究证明了HPCT水凝胶具有可逆的温度敏感性。值得注意的是，HPCT水凝胶可负载5 mg/mL的牛血清白蛋白并持续释放超过一周。此外，L929细胞毒性试验和大鼠体内降解试验证明，HPCT水凝胶具有良好的细胞相容性和组织相容性，且可在体内降解和吸收。在小鼠功能实验中，作为布鲁氏菌抗原的佐剂，HPCT水凝胶比明矾表现出更好的特异性抗体表达水平和细胞因子（白细胞介素-4、干扰素-γ）表达水平。因此，我们认为HPCT水凝胶在佐剂开发方面具有很大潜力。
