CD40L adjuvanted clade C DNA and MVA HIV vaccines

描述(由申请人提供)：在过去的三十年里，开发一种有效的艾滋病毒-1疫苗一直是一个难以实现的目标。因此，在全球范围内遏制由该病毒引起的疫情是一项重大挑战。泰国RV44药效试验的结果激发了人们对艾滋病毒疫苗开发的新的兴奋，并有力地支持了疫苗接种方法的开发，这种方法可以提高抗艾滋病毒环境抗体的效价和功能质量，从而可能显著增强对艾滋病毒的保护。该计划的总体目标是开发新的疫苗接种方法，不仅提高抗HIV细胞和体液免疫的数量，而且提高其功能质量。具体地说，我们建议将埃默里大学最近开发的两种新的疫苗接种方法结合起来，这两种方法在恒河猴身上显示出了巨大的前景。第一种方法使用表达在HIV VLP表面的树突状细胞(DC)和B细胞的共刺激分子CD40L作为遗传佐剂，以增强HIV特异性细胞和体液免疫的数量和功能质量，从而增强对获得SIV感染的保护。第二种方法使用一种新的缺乏4个免疫调节基因(MVAA4)的MVA作为疫苗载体，该载体显示恒河猴中HIV特异性细胞和体液免疫的数量显著增加。在这个项目中，我们希望将这两种新的互补方法结合起来，开发一种新的艾滋病毒疫苗接种策略。该项目将是埃默里大学(Amara博士、穆利根博士、Derdeyn博士和Velu博士)、NIH(Moss博士)、国际艾滋病疫苗倡议(Lavi；Dean博士)、沃尔特里德陆军研究所(WRAIR；Michael博士)、路易斯安那州立大学(LSU；Kozlowski博士)和疾控中心(Garber博士)的科学家共同努力的成果。该计划有3个项目和两个核心。拟议的计划建立在我们在临床前和临床环境中使用DNA和MVA疫苗的丰富经验以及在临床前模式中使用新疫苗的强大初步数据的基础上。该计划的成功完成将导致两种新疫苗产品和一种新型艾滋病毒疫苗的临床开发。

DESCRIPTION (provided by applicant): Development of an effective vaccine against HIV-1 has been an elusive goal for the past three decades. As a result it has been a major challenge to stem the tide of the epidemic caused by this virus globally. The results of the RV44 efficacy trial in Thailand have spurred a new level of excitement for the development of HIV vaccine and strongly support the development of vaccination approaches that enhance the titer and functional quality of anti-HIV Env antibody that may significantly enhance protection against HIV. The overall goal of this program is to develop novel vaccination approaches that not only enhance the magnitude but also enhance the functional quality of anti-HIV cellular and humoral immunity. Specifically, we propose to combine two new vaccination approaches developed recently at Emory University that showed great promise in rhesus macaques. The first approach uses CD40L, a co-stimulatory molecule for dendritic cells (DC) and B cells, expressed on the surface of HIV VLPs as a genetic adjuvant for enhancing the magnitude and functional quality of HIV-specific cellular and humoral immunity leading to enhanced protection from acquisition of SIV infection. The second approach uses a new MVA that lacks 4 immune modulatory genes (MVAA4) as a vaccine vector that showed a significant increase in the magnitude of HIV-specific cellular and humoral immunity in rhesus macaques. In this program, we hope to combine these two new complementary approaches to develop a novel vaccination strategy against HIV. This program will be a collaborative effort between scientists at the Emory University (Drs. Amara, Mulligan, Derdeyn, and Velu), NIH (Dr. Moss), International AIDS Vaccine Initiative (lAVI; Dr. Dean), Walter Reed Army Institute of Research (WRAIR; Dr. Michael), Louisiana State University (LSU; Dr. Kozlowski) and CDC (Dr. Garber). This Program has 3 projects and two cores. The proposed program builds upon the enormous experience with our DNA and MVA vaccines in the preclinical and clinical settings and strong preliminary data with the new vaccines in the preclinical model. Successful completion of the program will result in the clinical development of two new vaccine products and a novel HIV vaccine.