DENDRITIC CELL ACTIVATION BY ISS ODN FOR SIV IMMUNITY

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。 为艾滋病毒/艾滋病接种黏膜疫苗将为预防这一流行病提供一种解决办法。在这里，我们研究了扁桃体应用乙硫醇(AT-2)灭活的SIVmac239，结合B细胞和血浆细胞样树突状细胞(PDC)刺激CpG-C免疫刺激寡核苷酸(CpG-C ISS-ODN)作为佐剂的有效性。口腔白念珠菌感染对B细胞和PDCs的CpG-C ISS-ODN活性和PDCs的AT-2SIV活性无明显影响；CD80和CD86表达增加以及多种细胞因子和趋化因子，尤其是Th1吸引因子不影响PDCs的体外活性。为了测试CpG-C ISS-ODN是否通过激活局部PDCs和B细胞来增强免疫效果，将CpG-C ISS-ODN或对照ODN与AT-2 SIV一起应用于猕猴的扁桃体组织。动物在最后一次免疫后8周直肠接种致病SIVmac239之前，每6周接种5次疫苗。虽然在攻击前没有检测到T或B细胞反应，但与未免疫的对照组相比，AT-2SIV免疫显著降低了感染频率(p0.03)，即使在免疫动物的额外攻击之后也是如此。然而，CpG-C ISS-ODN处理的效果并不高于对照ODN。一旦动物被感染，就会检测到SIV特异性T细胞和抗体反应。这项工作首次证明AT-2SIV作为一种有前景的疫苗抗原应用于口腔粘膜相关淋巴组织，并对推进鼻咽部HIV疫苗接种具有重要意义。

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. Mucosal vaccination for HIV/AIDS would provide a preventative solution to the pandemic. Here, we examine the effectiveness of tonsillar application of aldrithiol 2 (AT-2) inactivated SIVmac239, in combination with the B cell and plasmacytoid dendritic cell (PDC) stimulus CpG-C immunostimulatory olinucleotides (CpG-C ISS-ODNs) as the adjuvant. In vitro CpG-C ISS-ODN activation of B cells and PDCs and AT-2 SIV activation of PDCs were not affected by the ubiquitous oral pathogen Candida albicans; elevated CD80 and CD86 expression and several cytokines and chemokines, in particular Th1-attracting factors. To test if CpG-C ISS-ODNs would enhance the effect of a mucosally applied vaccine by activating local PDCs and B cells to augment immunity, macaques had CpG-C ISS-ODNs or control ODNs applied with AT-2 SIV to the tonsillar tissues. Animals received 5 vaccinations every 6 weeks before being challenged rectally with pathogenic SIVmac239, 8 weeks after the last immunization. Although no T or B cell responses were detected prior to challenge, immunization with AT-2 SIV significantly (p0.03) reduced the frequency of infection compared to non-immunized controls, even after additional challenges of the immunized animals. However, there was no beneficial effect of the CpG-C ISS-ODN treatment above the control ODNs. SIV-specific T cell and antibody responses were detected once animals became infected. This work provides the first evidence for AT-2 SIV as a promising vaccine antigen when applied to the oral mucosal-associated lymphoid tissues and has important implications for the advancement of nasopharyngeal vaccination against HIV.