高效诱导2型免疫应答的降压疫苗呈递系统CpG ODN-VLP研究

Therapeutic vaccines such as Hypertension vaccine provide a new method for the treatment of chronic diseases, the key to its success is the efficient selective antigen-presenting system, which break immune tolerance to produce antigen-specific antibodies and play a role. Virus-like particles containing CpG ODNs(CpG ODN-VLP) is ideal delivery system for hypertension vaccine and other therapeutic vaccines. Based on efficiency and safety considerations, hypertension therapeutic vaccines need to be efficient to produce type 2 immune response against autoantigen without the risk of type 1 immune response,therefore the selection of appropriate diameter of VLP and the right kind of CpG ONDs is very necessary. This study choose the 95nm diameter 0305φ8-36 phage as the source of virus, application of gene recombinant methods to produce the corresponding VLP, which contains B-type of CpG ODNs. Then it couple with the L-type calcium channel peptide (CN8), which has already declared the national patent, to form the hypertension vaccine. Spontaneously hypertensive rats were immunized with the hypertension vaccine. Through the observation of antibody titers, indexes of the humoral and cellular immune reaction , blood pressure and pathological changes, we can assess the immune response type,efficiency, and security of the delivery system, in order to produce a type 2 immune response therapeutic vaccines presenting system, which is efficiency and safety, at the same time provide a suitable platform for hypertension therapeutic vaccine.

高血压疫苗等治疗性疫苗为治疗慢性疾病提供了新方法, 其成功的关键是选择高效的抗原呈递系统,打破免疫耐受，产生针对特定抗原的抗体并发挥作用，包裹CpG ODNs的病毒样颗粒（CpG ODN-VLP）即是高血压等治疗性疫苗的理想呈递系统。基于效率和安全考虑，高血压等治疗性疫苗需高效产生针对自身抗原的2型免疫应答而不发生1型免疫应答,选择合适直径的VLP和恰当类型的CpG ONDs十分必要。本研究选择直径为95nm的0305φ8-36噬菌体为源病毒，应用基因重组的方法，制备出相应的VLP,并包裹B型CpG ODNs，与申报着发明的L型钙通道短肽(CN8)耦联成高血压疫苗，分别免疫自发性高血压大鼠，观察抗体滴度、反应体液免疫和细胞免疫相关指标、血压和病理改变，以评估该呈递系统的免疫应答效率、类型和安全性,从而制备出一种2型免疫应答效率强且安全的治疗性疫苗呈递系统，为高血压疫苗等提供合适的平台。

高血压疫苗等治疗性疫苗为治疗慢性疾病提供了新方法, 其成功的关键是选择高效的抗原呈递系统,打破免疫耐受，产生针对特定抗原的抗体并发挥作用，包裹CpG ODNs的病毒样颗粒（CpG ODN-VLP）即是高血压等治疗性疫苗的理想呈递系统。基于效率和安全考虑，高血压等治疗性疫苗需高效产生针对自身抗原的2型免疫应答而不发生1型免疫应答,选择合适直径的VLP和恰当类型的CpG ONDs十分必要。本研究通过大量前期工作基础及数据比对，最终选择了选择平均粒径为30nm的AP205噬菌体为源病毒，应用基因重组的方法，制备出相应的AP205-VLP,并包裹B型CpG ODNs，与L型钙通道短肽(CN8)耦联成高血压疫苗（CpGODNs-AP205VLP-CN8），免疫自发性高血压大鼠，观察抗体滴度、反应体液免疫和细胞免疫相关指标、血压和病理改变，并与未包裹B型CpG ODNs的短肽疫苗（AP205VLP-CN8）相对比，评估该呈递系统的免疫应答效率、类型和安全性。结果表明，AP205VLP-CN8相比，CpGODNs-AP205VLP-CN8能更高效诱导生发中心形成，刺激特异性抗体产生，维持抗体滴度，持久降低血压，更好地保护靶器官，是一种2型免疫应答效率强且安全的治疗性疫苗呈递系统。