ENHANCED IMMUNOGENICITY OF CHIMERIC SHIV VLPS

这个子项目是许多利用 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。 开发和实施有效的艾滋病毒疫苗，防止感染，是控制疾病传播的合理方法。 用猴免疫缺陷病毒（SIV）感染恒河猴是人类HIV感染的最佳动物模型。 本项目的目的是在非人灵长类动物模型上确定病毒样颗粒（VLP）的免疫原性和嵌合流感血凝素（HA）SHIV VLP和CD 40 L/SHIV VLP的增强免疫原性，我们拟在恒河猴模型上研究和比较SHIV VLP、HASHIV VLP和CD 40 L/SHIV VLP的免疫原性，以证实从小鼠模型获得的免疫原性数据。 我们将在第0、1、2、3、10和27周鼻内免疫SHIV VLP、HASHIV VLP和CD 40 L/SHIV VLP。在接种前和接种后的几个时间点（0、5、10、12、24、27、29、32、40周）采集血液、粘膜分泌物（唾液、支气管肺泡灌洗液和粪便）。将在第0、12和40周采集腹股沟和腋窝淋巴结。将测试针对SIV Gag和HIV Env的ELISA抗体、跨不同HIV毒株的中和抗体以及针对SIV Gag和HIV Env的CTL应答，并与不同VLP免疫进行比较。我们预期在嵌合HNSHIV VLP和CD 40 L/SHIV VLP免疫的小鼠中将观察到增强的免疫应答。最终，从猴子模型中获得的信息将成为未来在人体试验中成功开发HIV疫苗的基础。

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. Development and implementation of an effective HIV vaccine that would prevent infection is a logical approach to controlling the spread of the disease. Infection of rhesus macaques with the simian immunodeficiency virus (SIV) is the best animal model for HIV infection in humans. The goal of this project is to determine the immunogenicity of virus-like particles (VLPs) and enhanced immunogenicity of chimeric influenza hemagglutinin (HA) SHIV VLPs and CD40L/SHIV VLPs on the non-human primate model, we propose to study and compare the immunogenicity of SHIV VLPs, HASHIV VLPs and CD40L/SHIV VLPs in the rhesus macaques model to confirm the immunogenicity data obtained from the mouse model. We will immunize SHIV VLPs, HASHIV VLPs, and CD40L/SHIV VLPs intranasally at 0,1 , 2, 3,10,and 27 weeks. Blood, mucosal secretions (saliva, broncho-alveolar lavages and feces) will be collected at several time points pre- and post-vaccination (0, 5, IO, 12, 24, 27, 29, 32, 40 wks). Inguinal and axillary lymph nodes will be collected at 0, 12 and 40 weeks. ELISA antibody to SIV Gag and HIV Env, neutralizing antibody across different HIV strains, and CTL responses to SIV Gag and HIV Env will be tested and compared with different VLPs immunization. We expect that enhanced immune responses will be observed in chimeric HNSHIV VLP and CD40L/SHIV VLP immunized mice. Ultimately, information obtained from the monkey model will form a basis for the future development of a successful HIV vaccine in human trials.