CD40 LIGAND AS ADJUVANT FOR RAISING PROTECTIVE ANTI-HIV AB BY DNA/MVA VACCINES

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。 最近，对DNA/MVA HIV/AIDS疫苗的研究表明，GM-CSF可以增强免疫动物直肠分泌物中抗病毒IgA的存在。目前疫苗学面临的挑战之一是在非肠道接种疫苗后引起粘膜反应。为了进一步探索GM-CSF作为黏膜佐剂的能力，我们研究了联合应用GM-CSF对脊髓灰质炎灭活疫苗诱导粘膜反应能力的影响。 与口服脊髓灰质炎病毒疫苗相比，灭活脊髓灰质炎疫苗在直肠分泌物中产生的抗病毒IgA要少得多。该项目的目标是测试GM-CSF是否也可以提高灭活脊髓灰质炎疫苗直肠分泌物中抗病毒IgA的存在。如果成功，这些研究将开启一种新的方法来增强灭活脊髓灰质炎疫苗引起的粘膜反应，这种疫苗比减毒活疫苗更安全。这些研究还将显示GM-CSF是否可以用于增强非肠道疫苗引发粘膜反应的能力。 脊髓灰质炎疫苗将用于接种12只之前用我们的DNA/MVA艾滋病毒/艾滋病疫苗免疫的恒河猴。其中8只动物在2006年9月接受了SIV-162P3的直肠内挑战。这些受到挑战的猴子已经将SIV-162P3控制在我们的检测水平以下，并重建了它们的肠道CD4T细胞。

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. Recently, work with DNA/MVA HIV/AIDS vaccines has shown that GM-CSFcan enhance the presence of anti-viral IgA in the rectal secretions of immunized animals. One of the current challenges of vaccacinology is to elicit mucosal responses following parenteral administration of vaccines. To further explore the ability of GM-CSF to serve as a mucusal adjuvant, we studied the effect of co-administration of GM-CSF on the ability of inactivated polio vaccine to elicit mucosal responses. Comparing to oral polio virus vaccine, the inactivated polio vaccine elicits much less anti-viral IgA in rectal secretions. The goal of the project is to test whether GM-CSF can also enhance the presence of anti-viral IgA in rectal secretions for the inactivated polio vaccine. If sucessful, the studies will open a new approach for enhancing the mucosal responses elicited by the inactivated polio vaccine, a vaccine that is safer than the live-attenuated vaccine. The studies will also show whether GM-CSF can be used to enhance the ability of an parenteral vaccine to elicit mucosal responses. The polio vaccine will be used to vaccinate 12 rhesus macaques that were previously immunized with our DNA/MVA HIV/AIDS vaccine. Eight of these animals were intrarectally challenged with SHIV-162P3 in September of 2006. These challenged monkeys have controlled SHIV-162P3 to below our level of detection and have reconstituted their gut CD4 T cells.