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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 最近，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。疫苗学目前的挑战之一是在肠胃外施用疫苗后引起粘膜反应。为了进一步探索GM-CSF作为粘膜佐剂的能力，我们研究了GM-CSF的共同施用对灭活脊髓灰质炎疫苗引起粘膜应答的能力的影响。 与口服脊髓灰质炎病毒疫苗相比，脊髓灰质炎灭活疫苗在直肠分泌物中释放的抗病毒IgA明显减少。该项目的目标是测试GM-CSF是否也可以增强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，这些研究将为增强灭活脊髓灰质炎疫苗引起的粘膜反应开辟一条新途径，这种疫苗比减毒活疫苗更安全。这些研究还将表明GM-CSF是否可用于增强胃肠外疫苗引发粘膜反应的能力。 脊髓灰质炎疫苗将用于接种12只恒河猴，这些恒河猴先前已接种了我们的DNA/MVA HIV/AIDS疫苗。2006年9月，对其中8只动物进行了SHIV-162P3直肠内攻毒。这些受攻击的猴子已经将SHIV-162P3控制在我们的检测水平以下，并重建了它们的肠道CD4 T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.