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

用于抗 HIV 抗体和 CTL 的鼻用 DNA/蛋白疫苗

• 批准号: 7958681
• 负责人: PAMELA ANN KOZLOWSKI
• 金额: $ 5.82万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958681
• 关键词: Adenovirus Vector; Adjuvant; Animals; Antibodies; Antigens; Blood; Computer Retrieval of Information on Scientific Projects Database; DNA; Drug Formulations; Enhancing Antibodies; Enzyme-Linked Immunosorbent Assay; Exhibits; Frequencies; Funding; Gagging; Grant; HIV Antibodies; Human; Immunization; Immunoglobulin A; Immunoglobulin G; Institution; Interferon Type II; Macaca mulatta; Methods; Monitor; Nose; Primates; Proteins; Research; Research Personnel; Resources; SIV; Serum; Source; Staining method; Stains; T-Lymphocyte; United States National Institutes of Health; Vaccination; Vaccines; Women' s Group; base; cytokine; cytokine receptor gp130; nonhuman primate; response

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：确定 Invaplex 是否可以在非人灵长类动物中作为基于鼻 DNA 或蛋白质的疫苗的佐剂。方法。三组雌性恒河猴在第 0、4 和 8 周用 SIV gp130 蛋白和 SHIV89.6 DNA 进行鼻腔免疫。在第2组和第3组中，DNA/蛋白质制剂分别与0.25mg和0.5mg Invaplex共同施用。五个月后，所有动物都用表达 SIV 抗原的腺病毒载体 (Ad-SIV) 进行鼻腔加强。 ELISA 用于定量血清和分泌物中的 SIV 抗体。细胞内细胞因子染色用于监测 T 细胞反应。结果：与第 1 组相比，第 3 组动物在第 3 次免疫后血清中的 SIV env 特异性 IgG 和分泌物中的 IgA 显着增加。第 3 组中针对 DNA 编码抗原的全身 IgG 和粘膜 IgA 也有所增强。在第 12 周，第 3 组还表现出分泌 IFN-g 的循环 SIV env 特异性 T 细胞的频率显着更高。第 2 组表现出与第 1 组或第 3 组没有显着差异的中间反应。Ad-SIV 鼻腔加强使第 3 组中的 SIV 特异性抗体升高程度显着高于第 1 组。所有组的血液中分泌 IFN-g 和 TNF-a 的 SIV env 和 gag 特异性 T 细胞的百分比相似。结论：Invaplex 可以辅助非人灵长类动物中抗体和 T 细胞对鼻蛋白免疫原的反应。 Invaplex 还可以增强鼻 DNA 疫苗接种后产生的抗体。 Invaplex 有可能用作人类鼻 DNA 疫苗和蛋白质疫苗的佐剂。