The Multi-omics Vaccine Evaluation (MOVE) Consortium

多组学疫苗评估 (MOVE) 联盟

• 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
• 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

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.

项目摘要 艾滋病毒疫苗是我们获得持久的保护性免疫力和结束艾滋病的最佳机会。 长达数十年的艾滋病大流行。为了获得成功，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递送 按顺序为了避免病毒逃逸，必须同时诱导至少2-3种不同特异性的bnAb。 因此，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，而不是免疫原的矩阵。 顺序构建可靠地诱导针对仅一个表位的宽度的单组免疫原是一种有效的方法。 艰巨的挑战成功地完成了难度指数更高的任务，即组装一个有粘性的免疫原， 矩阵将需要在速度和粒度上有重大改进，我们可以设计和评估 疫苗。在此，我们提出了一种解决方案：通过在免疫原的每个阶段嵌入多组学技术， 发展，我们可以解锁规模的革命性增长，同时提高深度和 我们的分析解决方案。多组学疫苗评估（MOVE）联盟汇集了多个 一个由专家调查员组成的学科团队，具有长期的富有成效的合作历史。我们的核心假设 深入整合先进的多组学方法， 管道将通过允许我们在多个国家同时操作来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 以及测试可靠地诱导广泛、持久免疫的互补免疫原基质。到 为了实现我们的目标，我们提出以下具体目标： 具体目的1：描述新型V2顶点聚焦Env三聚体的人免疫原性。 具体目标2：评估Q23引发的免疫应答、候选加强免疫原和递送 在人源化动物模型中的策略。 具体目标3：将Q23骨架开发成多表位引发免疫原。