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基于维生素E的水包油纳米乳液佐剂的构建增强了灭活伪狂犬病病毒疫苗的免疫原性。

Construction of vitamin E-based oil-in-water nano-emulsion adjuvant enhances immunogenicity of inactivated pseudorabies virus vaccine.

作者信息

Yin Wenzhu, Chang Chen, Zhu Yalu, Ma Fang, Wang Haiyan, Lu Yu, Tang Bo, Deng Bihua

机构信息

Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Science, Nanjing, 210014, PR China; GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, 225300, PR China.

Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Science, Nanjing, 210014, PR China.

出版信息

Virology. 2025 Sep;610:110616. doi: 10.1016/j.virol.2025.110616. Epub 2025 Jun 28.

Abstract

Despite being a common way to prevent infection with the pseudorabies virus (PRV), inactivated vaccines are less effective because of their poor immunogenicity. Adjuvants, as an important component of vaccines, can greatly boost and alter the immune response. In this study, a newly oil-in-water nano-emulsion adjuvant OEBB containing 20 % vitamin E, 30 % Tween-80, and 50 % 1,3-propylene didecanoate was easily prepared with a good thermal stability and biosafety. Combining an inactivated PRV (10 TCID50/20 μL) with OEBB, the inactivated OEBB/PRV nano-vaccine with the effective particle diameter of 194.01 ± 59.54 nm was formulated. It displayed a good temperature stability and maintained the particle size within 28 days. Then, the OEBB/PRV nano-vaccine was evaluated for its safety and immunization effect using mice and piglets. The results showed that the OEBB/PRV nano-vaccine significantly increased model animals' antibody and cytokines. The neutralizing antibody was higher than PRV alone but there was no significantly difference from commercial adjuvant ISA201. Moreover, the challenge protection rate can reach 80 %, which was obviously superior to that of ISA201 (70 %). Safety tests found no hemolytic side effects, no symptoms of PRV or significant toxic reactions, and no damage to organs. The OEBB could enhance the activation of antigen-presenting cells in the local injection skin to deliver the PRV antigen to nearby lymph nodes. This led to increase CD3 population and promote differentiation to CD4 and CD8, which ultimately induced humoral and cellular immunity. The as-prepared OEBB in this study is an effective adjuvant for PRV inactivated vaccine.

摘要

尽管灭活疫苗是预防伪狂犬病病毒(PRV)感染的常用方法,但由于其免疫原性较差,效果不太理想。佐剂作为疫苗的重要组成部分,可以极大地增强和改变免疫反应。在本研究中,一种新型的水包油纳米乳液佐剂OEBB很容易制备,它含有20%的维生素E、30%的吐温80和50%的1,3 - 二癸酸丙二醇酯,具有良好的热稳定性和生物安全性。将灭活的PRV(10 TCID50/20 μL)与OEBB结合,制备出有效粒径为194.01±59.54 nm的灭活OEBB/PRV纳米疫苗。它表现出良好的温度稳定性,在28天内保持粒径不变。然后,使用小鼠和仔猪对OEBB/PRV纳米疫苗的安全性和免疫效果进行了评估。结果表明,OEBB/PRV纳米疫苗显著提高了模型动物的抗体和细胞因子水平。中和抗体高于单独使用PRV的情况,但与商业佐剂ISA201相比无显著差异。此外,攻毒保护率可达80%,明显优于ISA201(70%)。安全性测试未发现溶血副作用、PRV症状或明显的毒性反应,也未对器官造成损害。OEBB可增强局部注射皮肤中抗原呈递细胞的活化,将PRV抗原递送至附近淋巴结。这导致CD3细胞群体增加,并促进其向CD4和CD8分化,最终诱导体液免疫和细胞免疫。本研究中制备的OEBB是PRV灭活疫苗的一种有效佐剂。

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