Development of Ad26/Env Vaccines for HIV

这一IPCAVD计划的目标是通过高度合作和 多方面的研究计划，涉及学术界和工业界的主要研究人员。我们的整体 假设优化的AD26/Env嵌合体疫苗将诱导高功能抗体， 将保护人类免受多个HIV-1分支的感染。这个项目的意义在于 潜在的实际开发安全有效的全球艾滋病毒-1疫苗，无与伦比的承诺 主要制药公司对这种HIV-1疫苗的支持，以及我们的重大科学进步的机会 了解免疫保护的相关因素。 在我们目前的IPCAVD计划(U19AI096040)中，我们已经开发了另一种血清型腺病毒载体， 生物信息优化的HIV-1马赛克抗原，以及稳定的Env gp140蛋白免疫原。我们已经展示了 AD26-Env/Gag/Pol Prime，Env gp140 Protein Boost(AD26/Env)疫苗提供了前所未有的 恒河猴对异源SIVmac251攻击后感染的保护作用 猴子，以及针对SIV-SF162P3挑战的强大保护。相关保护 由系统血清学确定的多功能抗体反应。我们还推出了AD26/Env， AD26/MVA和AD26/MVA/Env马赛克疫苗进入1/2a期临床试验在美国、东非、 南非和泰国。在未来5年的IPCAVD计划中，我们建议定义 和我们的主要AD26/Env疫苗方案在恒河猴中实现保护的机制，以 将我们的铅疫苗方案推进到2b/3期人体疗效研究，并开发一种 改进的下一代HIV-1候选疫苗。为了实现IPCAVD计划的目标，我们 提出以下项目和核心： 项目1.艾滋病毒AD26/Env疫苗的临床前开发 项目2.艾滋病毒AD26/Env疫苗的制造和临床开发 核心A.行政核心 核心B.免疫学核心 核心C.NHP核心

The goal of this IPCAVD program is to develop Ad26/Env vaccines for HIV-1 by a highly collaborative and multifaceted research program involving leading investigators in academia and industry. Our overall hypothesis is that an optimized Ad26/Env mosaic vaccine will induce highly functional antibodies that will protect humans against acquisition of multiple HIV-1 clades. The significance of this program is the potential actual development of a safe and effective global HIV-1 vaccine, the unparalleled commitment of a major pharmaceutical company to this HIV-1 vaccine, and the opportunity for major scientific advances in our understanding of immune correlates of protection. In our current IPCAVD program (U19 AI096040), we have developed alternative serotype adenovirus vectors, bioinformatically optimized HIV-1 mosaic antigens, and stable Env gp140 protein immunogens. We have shown that the Ad26-Env/Gag/Pol prime, Env gp140 protein boost (Ad26/Env) vaccine afforded unprecedented protective efficacy against acquisition of infection following heterologous SIVmac251 challenges in rhesus monkeys, as well as robust protection against SHIV-SF162P3 challenges. Protection correlated with polyfunctional antibody responses as determined by systems serology. We have also advanced the Ad26/Env, Ad26/MVA, and Ad26/MVA/Env mosaic vaccines into phase 1/2a clinical trials in the United States, East Africa, South Africa, and Thailand. Over the next 5 years of this IPCAVD program, we propose to define the extent and mechanism of protection achieved by our lead Ad26/Env vaccine regimen in rhesus monkeys, to advance our lead vaccine regimen into phase 2b/3 efficacy studies in humans, and to develop an improved next generation HIV-1 vaccine candidate. To accomplish the goals of this IPCAVD program, we propose the following Projects and Cores: Project 1. Preclinical Development of Ad26/Env Vaccines for HIV Project 2. Manufacturing and Clinical Development of Ad26/Env Vaccines for HIV Core A. Administrative Core Core B. Immunology Core Core C. NHP Core