A NASAL DNA/PROTEIN VACCINE FOR ANTI-HIV ANTIBODY AND CTL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 简介：艾滋病毒疫苗开发的一个优先事项是在艾滋病毒传播最频繁的生殖道和直肠产生抗病毒免疫反应。最近的数据表明，需要口服或直肠免疫才能在疫苗接受者中诱导最佳的肠道免疫。然而，口服疫苗必须防止胃酸和肠腔内的降解酶。目的：研究脂质体和肠溶胶囊双包埋疫苗在口服后是否能诱导免疫应答。方法：将含有SIV包膜蛋白和编码非感染性SHIV89.6P颗粒的DNA的阳离子脂质体冷冻干燥后放置在可抵抗十二指肠酸性pH而非中性pH的肠溶胶囊内。12只经鼻途径免疫的恒河猴于第0周和第6周用脂质体DNA/SIV Env蛋白胶囊口服免疫。结果/讨论：在第一次口服免疫后1个月，所有动物的血液中都观察到了对SIV env和Gag蛋白的强烈淋巴增殖反应。大多数动物在第1次免疫后产生SIV Env和GAG特异性T细胞的频率增加，而在第2次免疫后所有动物的SIV Env和GAG特异性T细胞产生干扰素-g和肿瘤坏死因子-α的频率均增加。SIV特异性粘膜或系统抗体没有增加。一种利用阳离子脂质体和肠溶胶囊的双重包埋策略可以成功地在小肠内传递DNA/蛋白质以诱导疫苗特异性T细胞。然而，产生肠道IgA反应将需要更大剂量的蛋白质或口服佐剂。应该进行旨在优化口服艾滋病毒疫苗的进一步研究，因为同时使用鼻腔和口服途径的方案比使用肌肉和鼻腔途径的方案更有可能在生殖道和直肠诱导保护性免疫。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: A priority in HIV vaccine development is to generate antiviral immune responses in the genital tract and rectum, where HIV transmission most frequently occurs. Recent data suggests that oral or rectal immunization will be required to induce optimal intestinal immunity in vaccine recipients. However, oral vaccines must be protected from stomach acid as well as degradative enzymes in the intestinal lumen. To determine if dual encapsulation of vaccine in liposomes and enteric-coated capsules can induce immune responses after oral delivery. Methods: Cationic liposomes containing SIV envelope protein and DNA encoding noninfectious SHIV89.6P particles were freeze-dried and placed inside enteric-coated capsules designed to resist acidic pH but not the neutral pH of the duodenum. Twelve rhesus macaques that had been previously immunized by the nasal route with SHIV DNA/SIV Env protein were orally-immunized on weeks 0 and 6 with a capsule containing liposomal DNA/protein. Results/Discussion: Strong lymphoproliferative responses to the SIV Env and Gag proteins were observed in blood of all animals 1 month after the 1st oral immunization. The frequencies of SIV Env- and Gag-specific T cells producing IFN-g and TNF-a were increased in the majority of animals after the 1st immunization, and in all animals after the 2nd immunization. There were no increases in SIV-specific mucosal or systemic antibodies. A dual encapsulation strategy utilizing cationic liposomes and enteric-coated capsules can be used successfully to deliver DNA/protein in the small intestine for induction of vaccine-specific T cells. However, generating intestinal IgA responses will require larger doses of protein or an oral adjuvant. Further studies aimed at optimizing oral HIV vaccines should be performed since regimens that utilize both the nasal and oral delivery routes are more likely to induce protective immunity in the genital tract and rectum than those that utilize the intramuscular and nasal routes.