多价HIV DNA疫苗小鼠免疫方案的优化研究以及蛋白转导结构域在HIV蛋白亚单位疫苗中的应用探索

发布时间：2018-01-10 17:27

本文关键词：多价HIV DNA疫苗小鼠免疫方案的优化研究以及蛋白转导结构域在HIV蛋白亚单位疫苗中的应用探索　出处：《中国协和医科大学》2007年硕士论文　论文类型：学位论文

【摘要】： DNA疫苗和蛋白亚单位疫苗是艾滋病疫苗的两种重要形式。本论文探讨了多价HIV DNA疫苗免疫小鼠的优化方案，并对蛋白转导结构域在艾滋病亚单位疫苗中的应用进行探索性研究。 HIV基因的高度变异是艾滋病疫苗研制过程中所面临的重大挑战。一个有效的艾滋病疫苗，不仅仅只是满足安全性和免疫原性方面的要求，还需要能广泛识别HIV的各种抗原并产生免疫应答。本文首先讨论了携带中国流行株CN54抗原的多价HIV DNA疫苗pGPNef和pGP140两质粒共同免疫小鼠后所诱导的细胞免疫应答。Env和Pol诱导的细胞免疫反应水平较强，质粒单独免疫效果较好，，两质粒混合免疫或分肢免疫均会使得细胞免疫应答水平有所降低。两质粒共同免疫时，两质粒分肢免疫的效果在一定程度上优于两质粒混合免疫；免疫3次是最优方案。融合蛋白转导结构域的蛋白或多肽能够高效进入细胞，并且被抗原呈递细胞以MHC-Ⅰ类分子途径进行加工处理。本研究在原核系统中，表达并纯化了融合Tat-PTD的HIV CN54抗原P24和Nef，并用这些重组蛋白免疫小鼠，评价免疫后小鼠的细胞免疫应答水平。然而，融合PTD的HIV P24和Nef重组抗原没有显著的细胞免疫原性。该方法为设计新一代的HIV蛋白亚单位疫苗提供了新思路。
[Abstract]:DNA vaccine and protein subunit vaccine are two important forms of AIDS vaccine. In this paper, we explored the optimized scheme of multivalent HIV DNA vaccine immunization in mice, and explored the application of protein transduction domain in HIV subunit vaccine.
The height variations of the HIV gene is a major challenge for AIDS vaccine development process. An effective AIDS vaccine, not just to meet the safety and immunogenicity of the requirements, but also requires a variety of antigens can be widely HIV recognition by the immune response. The cellular immune response level induced by firstly carrying Chinese popular strains of CN54 antigen and pGP140 pGPNef vaccine polyvalent HIV DNA two plasmid together after immunization of mice cellular immune response induced by Pol and.Env is stronger, better immunized with plasmid, plasmid or two hybrid immune component will make the immune cell immune response level decreased. The two plasmid co immunized two plasmid, immune component the effect to a certain extent better than two were mixed immunity; immunity 3 is the optimal solution.
The fusion protein transduction domain protein or polypeptide can efficiently enter cells, and antigen presenting cells processed by MHC- class I molecules approach. This study in prokaryotic system, the expression of Tat-PTD and HIV CN54 fusion antigen P24 and Nef were purified, and these recombinant protein immunized mice, evaluation of immunized mice the cellular immune response. However, HIV P24 and Nef recombinant antigen PTD fusion cells without immunogenicity significantly. This method provides a new idea for the design of a new generation of HIV protein subunit vaccine.

【学位授予单位】：中国协和医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R392

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