Development of Ad26/Env Vaccines for HIV

该IPCAVD计划的目标是通过高度协作和合作， 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 一种假设是，优化的Ad 26/Env嵌合体疫苗将诱导高度功能性的抗体， 将保护人类免受多种HIV-1进化枝的感染。该计划的意义在于， 安全有效的全球HIV-1疫苗的潜在实际开发， 主要的制药公司，这种艾滋病毒-1疫苗，并在我们的重大科学进步的机会， 了解免疫保护的相关性。 在我们目前的IPCAVD项目（U19 AI 096040）中，我们已经开发了替代血清型腺病毒载体， 生物信息学优化的HIV-1嵌合抗原和稳定的Env gp 140蛋白免疫原。我们已经表明 Ad 26-Env/Gag/Pol prime，Env gp 140蛋白加强（Ad 26/Env）疫苗提供了前所未有的 恒河猴在异源SIVmac 251攻击后对获得性感染的保护效力 猴，以及对SHIV-SF 162 P3攻击的强大保护。保护与 通过系统血清学测定的多功能抗体应答。我们还改进了Ad 26/Env， Ad 26/MVA和Ad 26/MVA/Env嵌合体疫苗在美国、东非、非洲、 南非和泰国。在未来5年的IPCAVD计划中，我们建议定义 和机制，我们的领导Ad 26/Env疫苗方案在恒河猴中实现的保护， 将我们的主要疫苗方案推进到2b/3期人体有效性研究，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。HIV Ad 26/Env疫苗的临床前研究进展 项目2. HIV Ad 26/Env疫苗的研制及临床应用 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