氢氧化铝佐剂制备工艺的建立及其在鼠疫疫苗中的免疫效果评价  

Establishment of preparation process of aluminum hydroxide adjuvant and evaluation of immune effect in plague vaccine

作　　者：李睿 张婷婷 吴智远 孙田华 马维民 李朋伟 高晶晶 郭海晨 慕艳红 焦磊 LI Rui;ZHANG Ting-ting;WU Zhi-yuan;SUN Tian-hua;MA Wei-min;LI Peng-wei;GAO Jing-jing;GUO Hai-chen;MU Yan-hong;JIAO Lei(The Third Research Department in Lanzhou Institute of Biological Products Co.,Ltd.,Center for Gansu Provincial Vaccine Engineering Research,Lanzhou 730046,Gansu Province,China)

机构地区：[1]兰州生物制品研究所有限责任公司第三研究室甘肃省疫苗工程技术研究中心,甘肃兰州730046

出　　处：《微生物学免疫学进展》2021年第5期29-34,共6页Progress In Microbiology and Immunology

基　　金：国家重点研发计划生物安全关键技术研发专项(2018YFC200602)。

摘　　要：目的建立氢氧化铝佐剂制备工艺,并吸附抗原配制鼠疫疫苗,对其进行免疫效果评价。方法采用氯化铝与氢氧化钠反应生成氢氧化铝胶体,通过优化制备工艺,制备出纳米级铝佐剂,并对其进行连续4批质量检测,将其与丹麦ALH铝佐剂在吸附率、沉降率、粒径、配制鼠疫疫苗安全性及免疫原性方面进行比较。结果 4批次氢氧化铝含量平均值为18.67 mg/mL,氯化钠含量平均值为29.60 mg/mL,平均pH为5.66;各批次氢氧化铝佐剂沉降率及吸附率检测结果均符合《中华人民共和国药典》2020版(四部)的检测要求;粒径控制已达到纳米级,平均值为100~600 nm;配制鼠疫疫苗安全性检测结果合格,20200404批铝佐剂与ALH铝佐剂分别配制鼠疫疫苗免疫NIH小鼠,20200404疫苗组V抗体IgG、IgG1抗体效价均高于ALH疫苗组,差异均有统计学意义(P<0.000 5);20200404疫苗组V抗体IgG2a抗体效价与ALH疫苗组差异无统计学意义(P>0.05);20200404疫苗组与ALH疫苗组F1抗体IgG、IgG1、IgG2a抗体效价差异均无统计学意义(P>0.05)。结论成功建立了氢氧化铝佐剂制备工艺,为制备鼠疫疫苗用铝佐剂奠定了基础。Objective To establish the preparation technology of aluminum hydroxide adjuvant and evaluate the immune effect in plague vaccine. Methods Al(OH)3 colloids were preparated by the reaction of aluminum chloride and sodium hydroxide. The nanometer aluminum adjuvant was prepared by optimizing the preparation process. The quality of the adjuvant was tested in four batches consecutively. It was compared with Danish ALH aluminum adjuvant in adsorption rate, deposition rate, particle size, safety and immunogenicity of vaccine prepatation. Results The test results showed that the average content of aluminum hydroxide adjuvant was 18.67 mg/mL, the average content of sodium chloride was 29.60 mg/mL, and the average pH value was 5.66. The sedimentation rate and adsorption rate test results of each batch of aluminum hydroxide adjuvant met the test requirements of Chinese Pharmacopoeia 2020 edition;the particle size control reached the nanometer level, and the average value of each batch was 100-600 nm;the safety test results of plague vaccine prepared by batch 20200404 and ALH aluminum hydroxide adjuvant were qualified.NIH mice were immunized with plague vaccine prepared by 20200404 batches of aluminum adjuvant and ALH aluminum adjuvant, respectively. The titers of anti-V IgG and IgG1 antibodies in 20200404 vaccine group were higher than those in ALH vaccine group, and the differences were statistically significant(P<0.000 5).There was no significant difference in the titer of anti-V IgG2 a antibody between 20200404 vaccine group and ALH vaccine group(P>0.05). There were no significant differences in the titer of anti-F1 IgG, IgG1 and IgG2 a antibodies between 20200404 vaccine group and ALH vaccine group(P>0.05). Conclusion The preparation process of aluminum hydroxide was successfully established, which laid a foundation for the preparation of aluminum adjuvanted plague vaccine.

关 键 词：氢氧化铝 佐剂 粒径 鼠疫疫苗 工艺优化 安全性 免疫原性 

分 类 号：R516.8[医药卫生—内科学]