摘要
目的:优化基于鼻腔黏膜免疫研究的乳液颗粒作为疫苗佐剂的制备配方及免疫评价效果。方法:以特定分子量和浓度的壳聚糖、PLGA以及商品铝佐剂经过不同配方制备,并与鸡卵清蛋白(Ovalbumin,OVA)混合,引入至油包水乳化液作为内部水相,再加入至含有Tween80的PBS的外水相中,形成3种W/O/W复合乳液佐剂;以小鼠动物作为模型,通过滴鼻进行了3种复乳佐剂的体内免疫效果评价实验。结果:使用分子量为1.3W的PLGA制备得到粒径为286 nm的均一颗粒作为水包油包颗粒的内水相,在针对鼻腔黏膜免疫效果评价实验中,证明PNP/O/W复乳能够有效延长鼻黏膜停留时间,血清中特异性IgG抗体滴度增加了20倍,鼻灌洗液中分泌型IgA的抗体水平提高了60倍以上,具有良好的体液和黏膜免疫效果。结论:使用了3种颗粒通过不同配方的制备作为内水相,成功将其引入至复乳后,在以小鼠为动物模型进行的免疫实验中,PLGA为颗粒的复合乳液佐剂有效提升了对小鼠的免疫效果,且具备较好的生物安全性,证明了PNP/O/W复合乳液佐剂能够作为良好的预防和治疗性疫苗佐剂。
Objective:To optimize the formulation for the preparation of emulsion particles as vaccine adjuvants based on nasal mucosal immunity studies and the immunological evaluation of their efficacy.Methods:Chitosan,PLGA and commercial aluminum adjuvant of specific molecular weight and concentration were prepared by different formulations and mixed with chicken ovalbumin(OVA),introduced into water-in-oil emulsion as the internal aqueous phase,and then added into the external aqueous phase of PBS containing Tween80 to form the three kinds of water-in-oil-in water(W/OW)P/O/W multiple emulsion adjuvants;the three kinds of compound emulsion adjuvants were evaluated in vivo using mouse animals as a model by The in vivo immunization effects of the three compound emulsion adjuvants were evaluated in mice by nose-dropping.RESULTS:Using PLGA with molecular weight of 1.3W to prepare homogeneous particles with particle size of 286 nm as the inner aqueous phase of the oil-in-water particles,it was proved that the PNP/O/W complex emulsions were able to effectively prolong the retention time of the nasal mucosa in the immunization experiments,and the titer of the specific IgG antibody in the serum increased by 20-fold,and the level of the antibody against secretory IgA in the nasal lavage increased by more than 60-fold,with good in vivo immunity effects.CONCLUSION:After using three kinds of particles prepared by different formulations as the internal aqueous phase and successfully introducing them into the compound emulsion,the compound emulsion adjuvant with PLGA particles effectively enhanced the immunization effect on mice in the immunization experiments using mice as the animal model,and the better biosafety,which also proved that the compound emulsion adjuvant of PNP/O/W could be used as a good adjuvant of the prophylactic and therapeutic vaccine.
作者
张超越
苗春宇
张豪
ZHANG Chaoyue;MIAO Chunyu;ZHANG Hao(Jiangxi Science and Technology Normal University,Nanchang Jiangxi 330013,China;State Key Laboratory of Biochemical Engineering,Key Laboratory of Biopharmaceutical Preparation and Delivery,Institute of Process Engineering,Chinese Academy of Sciences Beijing 100190,China)
出处
《江西化工》
2025年第4期69-74,95,共7页
Jiangxi Chemical Industry
基金
江西省自然科学基金(20232BAB204018)
江西科技师范大学博士科研启动基金(2020BSQD011)。
关键词
佐剂
水包油包水乳液
经鼻疫苗
免疫效果
adjuvant
oil-in-water emulsion
transnasal vaccine
immunization effect