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。 目的：确定Invaplex是否可以在非人灵长类动物中佐剂鼻腔DNA或蛋白质疫苗。方法：研究方法。用SIV gp130蛋白和SHIV89.6 DNA对3组雌性恒河猴分别于0、4、8周鼻腔免疫。在第2组和第3组中，DNA/蛋白质制剂分别与0.25 mg和0.5 mg Invaplex联合给药。5个月后，所有动物鼻腔注射表达SIV抗原的腺病毒载体(Ad-SIV)。用酶联免疫吸附试验检测血清和分泌物中的SIV抗体。细胞内细胞因子染色用于监测T细胞应答。结果：第3次免疫后，与第1组相比，第3组动物血清中SIV包膜特异性Ig G和分泌物中的Ig A均显著升高。在WK12，组3循环中SIV env特异性T细胞分泌干扰素-g的频率也显著高于对照组。第2组表现出与第1组或第3组无显著差异的中间反应。第3组鼻腔注射Ad-SIV后，SIV特异性抗体水平显著高于第1组。所有组的SIV包膜和GAG特异性T细胞在血液中分泌干扰素-g-和肿瘤坏死因子-α的百分比相似。结论：在非人灵长类动物中，Invaplex可以佐剂抗体和T细胞对鼻蛋白免疫原的应答。Invaplex还可以增强鼻腔DNA疫苗接种后产生的抗体。Invaplex可能会被用作人类鼻腔DNA和蛋白质疫苗的佐剂。

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. Objective: To determine if Invaplex can adjuvant nasal DNA- or protein-based vaccines in nonhuman primates. Methods. Three groups of female rhesus macaques were nasally immunized on weeks 0, 4, and 8 with SIV gp130 protein and SHIV89.6 DNA. In Groups 2 and 3, the DNA/protein formulation was co-administered with 0.25mg and 0.5mg Invaplex, respectively. Five months later, all animals were nasally boosted with adenovirus vectors expressing SIV antigens (Ad-SIV). ELISA was used to quantitate SIV antibodies in serum and secretions. Intracellular cytokine staining was used to monitor T cell responses. Results: When compared to Group 1, animals in Group 3 demonstrated significantly greater SIV env-specific IgG in serum and IgA in secretions after the 3rd immunization. Systemic IgG and mucosal IgA to DNA-encoded antigens were also enhanced in Group 3. On wk12, Group 3 also demonstrated significantly greater frequencies of circulating SIV env-specific T cells secreting IFN-g. Group 2 exhibited intermediate responses that did not differ significantly from Group 1 or 3. Nasal boosting with Ad-SIV elevated SIV-specific antibodies in Group 3 to a significantly greater extent than Group 1. All groups had similar percentages of SIV env- and gag-specific T cells secreting IFN-g- and TNF-a-secreting in blood. Conclusions: Invaplex can adjuvant antibody and T cell responses to nasal protein immunogens in nonhuman primates. Invaplex can also enhance antibody generated after nasal DNA vaccination. Invaplex could potentially be used as an adjuvant for both nasal DNA and protein vaccines in humans.