角鲨烯疫苗佐剂的研制及其佐剂性能研究

Q4 Medicine
E. Volosnikova, D. Shcherbakov, V. V. Ermolaev, N. V. Volkova, O. Kaplina, M. B. Borgoyakova, E. Danilenko
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引用次数: 0

摘要

现代亚单位疫苗的使用涉及在其组合物中引入佐剂。目前,寻找新的和改进现有的辅助系统正在积极进行中。以角鲨烯为基础的佐剂是众所周知的,并在许多国家批准用于流感疫苗的临床应用。本研究以角鲨烯为原料研制一种佐剂组合物。所得到的佐剂以含有亲水相和疏水相的油乳液形式组成。用频率为22千赫的超声波处理乳状液,使乳状液保持稳定。用电子显微镜检查所得乳剂的粒径。大多数颗粒(84%)的粒径在50-80 nm之间。对100只体重16-18 g的雄性Balb/C小鼠进行佐剂活性评价。为了评估体液免疫应答,进行了两次免疫接种,每只动物肌肉注射200 mL,间隔14天。用严重急性呼吸综合征冠状病毒2型(δ变异(B.1.617.2))表面S蛋白受体结合域(RBD)或鸡蛋卵清蛋白(OVA)作为抗原。RBD给药剂量为50 mg/只;OVA以两种剂量(1mg或5mg /只)施用。用氢氧化铝抗原作为阳性对照;生理盐水溶液作为阴性对照。采用重组SARS-CoV-2 s蛋白或鸡蛋卵白蛋白的RBD,通过ELISA检测小鼠血清中特异性抗体的效价来确定所获得的佐剂的有效性。结果表明,使用角鲨烯基佐剂可提高抗原的免疫原性。实验组抗RBD特异性抗体的平均滴度比氢氧化铝佐剂RBD免疫组高4倍。在实验ova组中,角鲨烯佐剂抗原的免疫原性也有所增加。因此,所开发的角鲨烯基佐剂组合物可以替代传统的基于铝盐的佐剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development of a vaccine adjuvant based on squalene and study of its adjuvant properties
The use of modern subunit vaccines involves adjuvant introduction into their composition. Currently, the search for new and improvement of existing adjuvant systems is actively underway. Squalene- based adjuvants are well-known and approved in a number of countries for clinical use in influenza vaccines. Our study was devoted to the development of an adjuvant composition on the basis of squalene. The resulting adjuvants were composed in a form of oil emulsion containing a hydrophilic and hydrophobic phase. The stability of the emulsion was achieved by treating it with ultrasound at a frequency of 22 kHz. Particle sizes of the obtained emulsions were examined with the use of an electron microscope. The particle size was calculated to be 50-80 nm for the majority of particles (84%). Adjuvant activity was evaluated in 100 male Balb/C mice, weighing 16-18 g. To assess the humoral immune response, immunization was performed twice, with a 14-day interval, by intramuscular injection of 200 mL per animal. The receptor-binding domain (RBD) of the surface S protein of the severe acute respiratory syndrome coronavirus 2 (Delta variant (B.1.617.2)) or ovalbumin (OVA) from chicken eggs were used as antigens. RBD was administered at a dose of 50 mg/animal; OVA was administered at two doses (1 mg or 5 mg/animal). An antigen with aluminum hydroxide was used as a positive control; a saline solution was used as a negative control. The effectiveness of the obtained adjuvants was determined by measuring the titers of specific antibodies in mouse sera in ELISA assays using the recombinant RBD of SARS-CoV-2 S-protein or ovalbumin from chicken eggs. It was shown that the use of squalene-based adjuvants increased the antigens’ immunogenicity. The average titers of specific antibodies against RBD in the experimental group were 4 times higher than in the group immunized with RBD adjuvanted with aluminum hydroxide. An increase in immunogenicity of the antigen adjuvanted with squalene was also observed in the experimental OVA-group. Thus, it was shown that the developed squalene-based adjuvant compositions could be an alternative to the traditional adjuvants based on aluminum salts.
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来源期刊
Medical Immunology (Russia)
Medical Immunology (Russia) Medicine-Immunology and Allergy
CiteScore
0.70
自引率
0.00%
发文量
88
审稿时长
12 weeks
期刊介绍: The journal mission is to promote scientific achievements in fundamental and applied immunology to various medical fields, the publication of reviews, lectures, essays by leading domestic and foreign experts in the field of fundamental and experimental immunology, clinical immunology, allergology, immunodiagnostics and immunotherapy of infectious, allergy, autoimmune diseases and cancer.
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