Adoptive transfer of immunity elicited by attenuated HIV vaccines

减毒艾滋病毒疫苗引发的过继性免疫转移

• 批准号: 7560022
• 负责人: David H. O'Connor
• 金额: $ 74.98万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7560022
• 关键词: AIDS Vaccines; Adoptive Transfer; Animals; Antibodies; Attenuated; Attenuated Vaccines; Cells; Disease; Dose; Future; HIV vaccine; Immune; Immune response; Immunity; Infection; Life; Lymphocyte; Lymphocyte Count; Macaca; Mediating; Modeling; Monkeys; Mus; Testing; Time; Upper arm; Vaccinated; Vaccine Research; Vaccines; Viral Load result; Virus; pathogen; prophylactic; public health relevance; research study; response; success

DESCRIPTION (provided by applicant): Live, attenuated virus strains are the most effective AIDS vaccines identified to date. The protective immune responses elicited by attenuated vaccines are unknown. We recently developed a monkey model in which immune cells can transferred between animals, allowing us to explore the immunological requirements for vaccine-mediated protection. Similar adoptive transfer experiments in mice have revolutionized our understanding of pathogen immunity but have been impossible to perform in monkeys. In this proposal, we test the hypothesis that lymphocytes from animals vaccinated with attenuated viruses are responsible for the success of attenuated vaccines. We will test this hypothesis by transferring variable numbers of lymphocytes from monkeys vaccinated with live, attenuated virus into vaccine naive recipients who will subsequently be infected with pathogenic virus. We anticipate that a dose-dependent relationship exists between the number of transferred lymphocytes and protection from pathogenic disease. If we find that a high dose (1 x 1010) total lymphocytes are protective, we will test progressively lower lymphocyte doses to determine the protective threshold. If high doses of transferred lymphocytes are not protective, we will attempt to augment protection by combining lymphocyte transfer with transfer of antibodies purified from attenuated vaccinees. Successful completion of these experiments will determine which immune responses are responsible attenuated-vaccine mediated protection, one of the most important questions in contemporary AIDS vaccine research. Moreover, demonstration that adoptive transfer studies are feasible in macaques will potentiate future studies examining the minimal immunological prerequisites for vaccine-mediated protection. PUBLIC HEALTH RELEVANCE: With the number of new infections rising faster than ever, a prophylactic vaccine for HIV is urgently needed. Live strains of virus, genetically modified to grow poorly, elicit the most effective immune responses ever witnessed in more than 20 years of testing. For the first time, we will attempt to transfer this immunity between animals in order to understand which arms of the immune response are involved in protection.

描述（由申请人提供）：现场直播病毒菌株是迄今为止确定的最有效的艾滋病疫苗。减毒疫苗引起的保护性免疫反应尚不清楚。我们最近开发了一种猴子模型，其中免疫细胞可以在动物之间转移，从而使我们能够探索疫苗介导的保护的免疫学要求。小鼠中的类似收养转移实验彻底改变了我们对病原体免疫的理解，但在猴子中不可能进行。在该提案中，我们检验了以下假设：从衰减病毒接种的动物的淋巴细胞是导致疫苗成功的成功。我们将通过转移来自活的，衰减病毒接种的猴子的淋巴细胞数量来检验这一假设，这些猴子随后将被致病病毒感染。我们预计，转移的淋巴细胞数量与致病性疾病的保护之间存在剂量依赖性关系。如果我们发现高剂量（1 x 1010）总淋巴细胞具有保护性，我们将逐渐测试较低的淋巴细胞剂量以确定保护阈值。如果高剂量转移的淋巴细胞不是保护性的，我们将尝试通过将淋巴细胞转移与从减毒疫苗中纯化的抗体转移相结合来增强保护。这些实验的成功完成将确定哪些免疫反应是负责减弱疫苗的介导的保护，这是当代艾滋病疫苗研究中最重要的问题之一。此外，证明了猕猴中的收养转移研究是可行的，这将增强未来的研究，以研究疫苗介导的保护的最低免疫学先决条件。公共卫生相关性：随着新感染的数量比以往任何时候都要快，因此迫切需要一种预防艾滋病毒的预防性疫苗。病毒的活菌株，经过基因修饰以生长较差，引起了20多年的测试中见证的最有效的免疫反应。我们将第一次尝试转移动物之间的这种免疫力，以了解免疫反应的哪些臂参与保护。