The Multi-omics Vaccine Evaluation (MOVE) Consortium

多组学疫苗评估 (MOVE) 联盟

基本信息

批准号：
10725048
负责人：
Bryan Briney
金额：
$ 179.85万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10725048
关键词：
Acceleration Acquired Immunodeficiency Syndrome Animal Model Antibodies Antibody Response Antibody Specificity Antigens Apical B cell repertoire B-Lymphocytes Cells Collaborations Development Epitopes Evaluation Frequencies Genetic Goals HIV HIV Antibodies HIV vaccine Human Immune response Immunity Immunization Individual Informatics Mission Pattern Polysaccharides Productivity Proliferating Proteomics Protocols documentation Recording of previous events Research Personnel Resolution Series Serum Site Specificity Speed Techniques Technology Testing Tissues Vaccines Vertebral column Viral computerized tools design human monoclonal antibodies humanized mouse immunogenicity improved innovation multidisciplinary multiple omics neutralizing antibody novel pandemic disease parallelization tool vaccine development vaccine evaluation

项目摘要

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.

项目概要 HIV 疫苗是我们激发持久的保护性免疫力并结束艾滋病毒流行的最佳机会。长达数十年的艾滋病流行。为了取得成功，基于抗体的 HIV 疫苗必须可靠地广泛诱导中和抗体 (bnAbs)，最有可能通过一系列免疫原或免疫原混合物提供依次。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 bnAb。因此，从更全面的角度来看，HIV 疫苗成分将类似于免疫原矩阵，而不是免疫原矩阵。顺序。构建一套能够可靠地诱导针对一个表位的广度的免疫原是一种艰巨的挑战。成功完成难度指数级更高的组装粘性免疫原的任务矩阵将需要显着提高我们设计和评估的速度和粒度疫苗。在这里，我们提出了一个解决方案：通过在免疫原的每个阶段嵌入多组学技术发展，我们可以在规模上实现革命性的增长，同时提高深度和我们的分析的分辨率。多组学疫苗评估 (MOVE) 联盟汇集了多组学专家由具有悠久富有成效的合作历史的专家调查员组成的学科团队。我们的中心假设是在我们的迭代疫苗开发过程中深度整合先进的多组学方法管道将允许我们同时跨多个项目进行操作，从而加速艾滋病毒疫苗的发现免疫原。我们的总体使命是通过并行设计加速艾滋病毒疫苗的开发以及测试可靠诱导广泛、持久免疫力的互补免疫原基质。到为了实现我们的目标，我们提出以下具体目标：具体目标 1：分析新型 V2 顶端聚焦 Env 三聚体的人类免疫原性。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中的策略。具体目标 3：将 Q23 主链开发成多表位引发免疫原。