NASAL VACCINES FOR PREVENTION OF HIV INFECTION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们研究的目标是测试潜在的疫苗和佐剂制剂在鼻腔内的安全性和免疫原性。特别是，我们正在寻找在女性生殖道和直肠产生强大的艾滋病毒特异性免疫反应的产品，这些粘膜组织在感染后充当主要的艾滋病毒储存库。在这些部位诱导抗病毒反应的疫苗应该比目前的肌肉注射疫苗更有效，后者主要在非粘膜间隔诱导反应。我们之前已经证明，鼻腔接种是在女性生殖道和直肠产生免疫反应的最佳途径。然而，可用于增强对艾滋病毒鼻腔疫苗的免疫反应的佐剂尚未被确定用于人类。在过去的一年里，我们测试了一种潜在的鼻佐剂QS-21皂苷衍生物的安全性和佐剂性。猕猴鼻腔注射10或25微克QS-21和重组HIV gp41蛋白，没有产生任何局部或全身不良反应。此外，鼻腔接种gp41加25微克QS-21的动物与单独接种gp41的动物相比，血液和阴道粘膜中分泌gp41特异性干扰素-伽马和IL-2的CD8和CD4T细胞的比例显著增加。接下来将测试QS-21增强黏膜对鼻腔艾滋病毒DNA疫苗的反应的能力。这些研究应有助于开发预防艾滋病毒感染的疫苗。

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. The goal of our studies is to test potential vaccine and adjuvant formulations for safety and immunogenicity in the nasal cavity. In particular, we are seeking products that produce strong HIV-specific immune responses in the female genital tract and rectum, mucosal tissues which serve as major HIV reservoirs after infection. Vaccines which induce antiviral responses at these sites should be more effective than current intramuscular vaccines which primarily induce responses in nonmucosal compartments. We have previously shown that the nasal vaccination route is best for producing immune responses in both the female genital tract and rectum. However, adjuvants which could be used to enhance immune responses to HIV nasal vaccines have not yet been identified for humans. In this past year, we tested the safety and adjuvanticity of a potential nasal adjuvant, the QS-21 saponin derivative. Nasal co-administration of 10 or 25 ug QS-21 with a recombinant HIV gp41 protein in rhesus macaques did not produce any local or systemic adverse reactions. In addition, animals nasally vaccinated with gp41 plus 25 ug QS-21 developed significantly greater proportions of gp41-specific IFN-gamma- and IL-2-secreting CD8 and CD4 T cells in blood and vaginal mucosa when compared to animals vaccinated with gp41 alone. The ability of QS-21 to augment mucosal responses to nasal HIV DNA vaccines will next be tested. These studies should facilitate the development of vaccines which prevent HIV infection.