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目的制备SIVmac239恒河猴(Macaca mulatta)细胞适应株病毒,模拟HIV性传播感染特点进行恒河猴直肠黏膜感染研究,探索引起系统性感染的病毒阈值水平与机体病毒、免疫学之间相关性,为我国艾滋病黏膜疫苗等生物制剂有效性评价提供新的模型构建思路。方法参照HIV性传播自然感染剂量范围,选用SIVmac239连续升高的3种剂量直肠黏膜途径感染两只恒河猴,采取多种方法进行病毒血症和免疫反应特点分析。结果两只恒河猴经2×101TCID50和2×102TCID50病毒滴度2次攻击后45d,经检测均未建立系统性感染,病毒特异性免疫反应均为阴性;第3次2×103TCID50病毒滴度攻击后,M296猴表现出典型的系统性感染特点,并诱导特异性免疫反应。结论确认了HIV性传播过程中的病毒剂量效应关系,为预防性生物制剂的猴体有效性评价提供了新的思路。同时,发现SIVmac239Gag区特异性的T细胞免疫反应在病毒控制过程中发挥了关键作用,对于新一代艾滋病黏膜疫苗的抗原选择具有指导性意义。
Objective To prepare Macaca mulatta cell-adapted strains of SIVmac239 and simulate the characteristics of HIV infection in rhesus monkeys for the study of rectal mucosal infections, and to explore the correlation between the viral threshold level and systemic virus and immunology in systemic infection, It provides a new idea of building a model for the evaluation of the effectiveness of biological agents such as AIDS mucosal vaccine in China. Methods According to the dose range of natural transmission of HIV infection, two Rhesus macaques were infected by three consecutive doses of SIVmac239, and the viremia and immune response were analyzed by a variety of methods. Results No systemic infection was found after 2 × 101TCID50 and 2 × 102TCID50 virus titers were detected in the two rhesus monkeys 2 times after challenge. The virus-specific immunoreactions were all negative. The third titers of 2 × 103TCID50 After challenge, M296 monkeys showed typical systemic infections and induced specific immune responses. Conclusions The dose-response relationship of virus in the process of sexual transmission of HIV was confirmed, which provided a new idea for the evaluation of the effectiveness of prophylactic monkeys. At the same time, it was found that the SIVmac239Gag region-specific T cell immune response plays a key role in virus control and is of guiding significance for the antigenic selection of a new generation of AIDS mucosal vaccines.