TARGETED DNA DELIVERY FOR SALIVARY IGA RESPONSES

描述(改编自《调查者摘要》)：裸露DNA疫苗 显示出通过任一T辅助(Th)1细胞发展保护性免疫的前景 或Th2细胞依赖的反应。然而，交付主要是有限的 外周部位而不是粘膜组织。因此，最小 分泌型(S)-免疫球蛋白A反应或免疫黏膜Th细胞。至 要成功地免疫粘膜，就必须考虑到 粘膜表面，并有效地靶向粘膜诱导组织。在一个 为了促进口腔内最佳的粘膜免疫，研究 建议利用一种DNA递送系统，借此表达质粒 与M细胞靶向分子复合，将DNA运送到粘膜 鼻腔诱导组织(I.N.)免疫接种。很像现场直播 通过M细胞介导宿主进入的载体疫苗递送系统，它是 假设M细胞配体，呼肠孤病毒蛋白Sigma 1，将指导 鼻腔相关淋巴组织(NALT)和共享淋巴组织的DNA 唾液相关淋巴组织(SALT)用于适当的刺激 粘膜B和T细胞亚群。因此，这项提案的目标是 测试这种新型疫苗递送系统在促进 唾液S-Ig A和Ig G抗体反应。为了进一步推动这一努力，在 具体目标1集中在评估粘膜的类型和大小 静脉注射诱导的抗体反应和支持性CD4+T细胞。 蛋白Sigma-1导向的DNA疫苗免疫。具体的研究 目标2的重点是优化盐对CTL的反应。对于特定的目标3， 以避免诱导中和抗体的可能性 来自Ulex uropaeus的M细胞凝集素Sigma 1将被检测其 将DNA疫苗运送到粘膜诱导组织诱导的能力 抗原特异性唾液抗体应答及其支持性CD4+T细胞 细胞。将进行的最后一组研究将评估 GM-CSF或IL-18与疫苗共免疫小鼠的实验研究 将改善粘膜免疫球蛋白A应答和粘膜CTL应答。这些研究 将为未来亚单位疫苗的开发提供基础，以针对 NALT用于在口腔和盐中激发保护性免疫。

DESCRIPTION (Adapted from the Investigator's Abstract): Naked DNA vaccines have shown promise for developing protective immunity by either T helper (Th)1 cell or Th2 cell-dependent responses. However, delivery has been primarily limited to peripheral sites rather than mucosal tissues. Consequently, minimal secretory (s)-IgA responses or immune mucosal Th cells are manifested. To successfully immunize the mucosa, efforts must consider the natural barriers at mucosal surfaces, and effectively target mucosal inductive tissues. In an effort to facilitate optimal mucosal immunity in the oral cavity, studies are proposed to utilize a DNA delivery system whereby the expression plasmid is complexed with a M cell-targeting molecule to ferry the DNA to mucosal inductive tissues following intranasal (i.n.) immunization. Much like live vector vaccine delivery systems which mediate host entry via M cells, it is hypothesized that the M cell ligand, reovirus protein sigma 1, will direct the DNA to the nasal-associated lymphoid tissue (NALT) and shared lymph nodes of the salivary-associated lymphoid tissues (SALT) for the appropriate stimulation of mucosal B and T cell subsets. Thus, the objective for this proposal is to test the effectiveness of this novel vaccine delivery system in promoting salivary s-IgA and IgG antibody responses. To further this effort, studies in Specific Aim 1 are focused in assessing the types and magnitude of mucosal antibody responses and the supportive CD4+ T cells induced following i.n. immunization with the protein sigma 1-directed DNA vaccine. Studies in Specific Aim 2 are focused on optimizing CTL responses by the SALT. For Specific Aim 3, to circumvent the possibility of inducing neutralizing antibodies against protein sigma 1, the M cell lectin from Ulex europaeus, will be tested for its ability to ferry the DNA vaccine to mucosal inductive tissues to elicit antigen-specific salivary antibody responses as well as their supportive CD4+ T cells. The last set of studies to be conducted will assess whether the incorporation of GM-CSF or IL-18 cDNA to co-immunize mice with the vaccine cDNA will improve mucosal IgA responses and mucosal CTL responses. These studies will provide the basis for future development of subunit vaccines to target the NALT for eliciting protective immunity in the oral cavity and SALT.