Sharpe Sally, Hanke Tomás, Tinsley-Bown Anne, Dennis Mike, Dowall Stuart, McMichael Andrew, Cranage Martin
Health Protection Agency, Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.
Virology. 2003 Aug 15;313(1):13-21. doi: 10.1016/s0042-6822(03)00282-4.
Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 microm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01(+) rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals.
全身给药编码重组人免疫缺陷病毒（HIV）衍生免疫原的DNA可有效激发猕猴的细胞毒性T淋巴细胞（CTL）反应。在这项进一步的初步研究中，我们评估了DNA的黏膜给药作为一种替代激发策略。将编码多CTL表位基因的质粒DNA pTH.HW掺入直径小于10微米的聚（D，L-乳酸-共-乙醇酸）微粒中。对2只Mamu-A*01(+)恒河猴进行5次直肠内免疫未能刺激产生循环疫苗特异性CTL反应。然而，在用同源改良安卡拉痘苗病毒疫苗MVA.HW进行皮内免疫1周后，在两只动物中均检测到CTL反应，该反应持续至最后一次加强免疫后12周的尸检分析时。相比之下，单独接种MVA构建体的动物中观察到较弱且持续时间较短的反应。对淋巴组织的分析显示，在两只经黏膜激发的动物的外周和区域淋巴结而非脾脏中存在弥散性CTL反应。
