The Multi-omics Vaccine Evaluation (MOVE) Consortium

项目总结 艾滋病毒疫苗是我们激发持久的保护性免疫并结束 数十年的艾滋病大流行。为了取得成功，基于抗体的艾滋病毒疫苗必须可靠地广泛诱导 中和抗体(BNAbs)，很可能是通过一系列免疫原或免疫原混合物传递的 按顺序进行。为了避免病毒逃逸，必须同时诱导至少2-3种不同特异性的bNAbs。 因此，对艾滋病毒疫苗组成的更全面的看法将类似于免疫原的矩阵，而不是 序列。构建一组仅针对一个表位可靠地诱导广度的免疫原是一种 艰巨的挑战。成功地完成了难度成倍增长的凝聚性免疫原组装任务 矩阵将要求我们在设计和评估时的速度和粒度方面有显著改进 疫苗。在这里，我们提出了一个解决方案：在免疫原的每个阶段嵌入多组学技术 发展，我们可以释放革命性的规模增长，同时提高深度和 解决我们的分析问题。多OMICS疫苗评估(MOVE)联盟汇集了多个 具有长期卓有成效合作历史的专业调查人员组成的纪律团队。我们的中心假设 在我们迭代的疫苗开发过程中深度整合先进的多组学方法 流水线将通过允许我们同时在多个 免疫原。我们的总体任务是通过并行设计来加速艾滋病毒疫苗的开发 以及检测可靠地诱导广泛、持久免疫的补充性免疫原矩阵。至 为了实现我们的目标，我们提出了以下具体目标： 具体目标1：分析一种新型V2顶端聚焦的Env三聚体的人体免疫原性。 具体目标2：评估Q23引发的免疫反应、候选增强免疫原和递送 人性化动物模型的策略。 具体目标3：将Q23主干发展成为多表位启动免疫原。

PROJECT SUMMARY An HIV vaccine represents our best opportunity for eliciting durable, protective immunity and ending the decades-long AIDS pandemic. To be successful, an antibody-based HIV vaccine must reliably induce broadly neutralizing antibodies (bnAbs), most likely via a series of immunogens or mixtures of immunogens delivered sequentially. To avoid viral escape, bnAbs of at least 2-3 distinct specificities must be induced concurrently. Thus, a more holistic view of HIV vaccine composition would resemble a matrix of immunogens rather than a sequence. Constructing a single set of immunogens that reliably induce breadth against just one epitope is a daunting challenge. Succeeding in the exponentially more difficult task of assembling a cohesive immunogen matrix will require significant improvements in the speed and granularity with which we can design and evaluate vaccines. Here, we propose a solution: by embedding multi-omics technology at each stage of immunogen development, we can unlock a revolutionary increase in scale while simultaneously improving the depth and resolution of our analyses. The Multi-Omics Vaccine Evaluation (MOVE) Consortium brings together a multi- disciplinary team of expert investigators with a long history of productive collaboration. Our central hypothesis is that deeply integrating advanced multi-omics approaches throughout our iterative vaccine development pipeline will speed the discovery of an HIV vaccine by allowing us to operate concurrently across multiple immunogens. Our overall mission is to accelerate development of an HIV vaccine by parallelizing the design and testing of a matrix of complementary immunogens that reliably induce broad, durable immunity. To accomplish our objectives, we propose the following Specific Aims: Specific Aim 1: Profile the human immunogenicity of a novel V2 apex-focusing Env trimer. Specific Aim 2: Evaluate Q23-elicited immune responses, candidate boosting immunogens, and delivery strategies in humanized animal models. Specific Aim 3: Develop the Q23 backbone into a multi-epitope priming immunogen.