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白细胞介素-2 与 VP60 共表达在减毒鼠伤寒沙门氏菌口服疫苗中的佐剂效应,用于预防兔病毒性出血症。

Adjuvant effects of interleukin-2 co-expression with VP60 in an oral vaccine delivered by attenuated Salmonella typhimurium against rabbit hemorrhagic disease.

机构信息

College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.

College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.

出版信息

Vet Microbiol. 2019 Mar;230:49-55. doi: 10.1016/j.vetmic.2019.01.008. Epub 2019 Jan 8.

Abstract

Rabbit hemorrhagic disease (RHD) is a highly contagious infection that has caused significant damage to the rabbit industry since 1984. Inactivated vaccines, the currently used prevention measures, are effective in controlling RHD. However, these vaccines are derived from the livers of infected rabbits, which constitutes a major concern in terms of animal welfare and safety. Administration of DNA vaccines in collaboration with appropriate adjuvants, in particular, cytokines, to strengthen the immune response presents a novel optimization strategy to generate more efficient vaccines. In this study, the adjuvant effect of interleukin (IL)-2 co-expression with the VP60 gene in a DNA vaccine was evaluated. In total, four groups of 60 RHD virus (RHDV)-free rabbits (30 days old) were orally or subcutaneously administered recombinant SL7207-pVAX1-IL2-VP60, SL7207-pVAX1-VP60, SL7207-pVAX1 bacteria or the commercial inactive vaccine, and the induced immunity evaluated by challenge with the RHDV(Y8504/China) strain on day 56. The Recombinant SL7207-pVAX1-IL2-VP60 induced a higher level of antibodies than the vaccine SL7207-pVAX1-VP60 and inactivated vaccines to a significant extent. The concentrations of interleukin (IL)-4 were markedly higher than those in groups immunized with the naked or inactive vaccine alone. Furthermore, the fusion gene vaccine provided higher protection (93.33%) after virus challenge relative to immunization with the single gene (SL7207-pVAX1-VP60). The collective results indicate that recombinant SL7207-pVAX1-IL-2-VP60 bacteria exert enhanced protective effects against RHDV and therefore present a strong candidate as a potential vaccine. Moreover, IL-2 enhanced both humoral and cellular responses, highlighting the utility of rabbit IL-2 as an effective adjuvant.

摘要

兔出血症(RHD)是一种高度传染性感染,自 1984 年以来对兔业造成了重大损害。目前使用的灭活疫苗是控制 RHD 的有效措施。然而,这些疫苗是从感染兔子的肝脏中提取的,这在动物福利和安全方面构成了一个主要问题。与适当的佐剂(特别是细胞因子)联合使用 DNA 疫苗来增强免疫反应,是一种产生更有效疫苗的新的优化策略。在这项研究中,评估了白细胞介素(IL)-2 与 VP60 基因共表达在 DNA 疫苗中的佐剂效应。总共将 60 只无 RHD 病毒(RHDV)的兔子(30 天大)分为 4 组,通过口服或皮下注射重组 SL7207-pVAX1-IL2-VP60、SL7207-pVAX1-VP60、SL7207-pVAX1 细菌或商业灭活疫苗,然后在第 56 天用 RHDV(Y8504/China)株攻毒评估诱导的免疫反应。与 SL7207-pVAX1-VP60 和灭活疫苗相比,重组 SL7207-pVAX1-IL2-VP60 诱导的抗体水平更高。与单独免疫裸疫苗或灭活疫苗相比,IL-4 的浓度明显更高。此外,与单一基因(SL7207-pVAX1-VP60)免疫相比,融合基因疫苗在病毒攻毒后提供了更高的保护率(93.33%)。研究结果表明,重组 SL7207-pVAX1-IL-2-VP60 细菌对 RHDV 具有增强的保护作用,因此是一种有潜力的疫苗候选物。此外,IL-2 增强了体液和细胞反应,凸显了兔 IL-2 作为有效佐剂的作用。

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