Strategies for Therapeutic Vaccination Against KSHV

KSHV 治疗性疫苗接种策略

• 批准号: 7852170
• 负责人: TIMOTHY N BULLOCK
• 金额: $ 50万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7852170
• 关键词: AIDS related cancer; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adoptive Transfer; Antibodies; Biological Models; CD4 Positive T Lymphocytes; CD8B1 gene; Cancer Etiology; Cell Count; Cells; Cessation of life; Coculture Techniques; Collaborations; Communicable Diseases; Country; Cytolysis; Developed Countries; Developing Countries; Development; Disease; Employment Opportunities; Epitopes; Etiology; Face; Family; Goals; Grant; Growth; HIV; HIV therapy; HLA-A2 Antigen; Herpesviridae; Herpesviridae Infections; Highly Active Antiretroviral Therapy; Human Herpesvirus 8; Immune; Immune response; Immune system; Immunity; Immunization; Immunocompetent; Immunocompromised Host; Immunologics; In Vitro; Individual; Kaposi Sarcoma; Laboratories; Lead; Lymphoma; Malignant Neoplasms; Measures; Memory; Modeling; Molecular; Multicentric Angiofollicular Lymphoid Hyperplasia; Mus; Nature; Non-Hodgkin' s Lymphoma; Oncogenic; Pathologic; Patients; Pattern; Pattern recognition receptor; Peptides; Pre-Clinical Model; Proteins; Protocols documentation; Research; Scheme; System; T-Lymphocyte; T-Lymphocyte Epitopes; TNFRSF5 gene; Target Populations; Testing; Therapeutic; Transgenic Mice; Vaccination; Vaccine Antigen; Vaccines; Viral; Virus; Virus Diseases; clinically relevant; combinatorial; effusion; fighting; immunogenicity; in vivo; novel; pathogen; patient population; prevent; programs; public health relevance; reconstitution; response; therapeutic vaccine; tumor; tumor growth; vaccination strategy; vaccine development

DESCRIPTION (provided by applicant): The goal of our project is to develop vaccine strategies that will target viral pathogens underlying the most common AIDS malignancies even in the unfavorable immunologic setting of low CD4+ T cell counts that typically characterizes HIV-infected patients. In this proposal, we have chosen as our model target Kaposi's sarcoma (KS)-associated herpesvirus (KSHV or HHV8), the etiologic agent of KS, primary effusion lymphoma and multicentric Castleman's disease. Specifically, we will identify relevant CD8+ T cell epitopes from gene products of KSHV and develop vaccination schemes that will elicit effector and memory CD8+ T cells specific for these epitopes. This project has the potential to provide relevant targets for the vaccination of vulnerable patient populations or the adoptive transfer therapy of afflicted individuals, and evidence for the efficacy of novel vaccination approaches in immunocompromised patients. This application is highly relevant to the goals of the RFA and, thus, more suitable for the Grand Opportunities solicitation rather than the Challenges Grant: It will provide the opportunity to expand a nascent but already fruitful cross- disciplinary collaboration between the Kedes and Bullock laboratories, leading to the identification of vaccine targets, a novel model system to test the relevance of the selected targets and the efficacy of the vaccination approaches being studied (potentially validating their use for multiple malignancies and disease states associated with immunocompromised individuals), and immediate new employment opportunities with additional ones as the program grows. PUBLIC HEALTH RELEVANCE: People with HIV/AIDS are unable to fight off many infectious diseases, including specific viruses that can cause cancers. Despite good HIV therapy available in relatively wealthy countries such as the U.S. and other developed nations, nearly one third of all deaths in AIDS patients are due to cancer and one half of these are caused by one of two viruses, EBV and lesser known one, KSHV. In the research that we are proposing, we are focusing on KSHV, which causes Kaposi's sarcoma, the single most common AIDS-related cancer. It is our hope to develop a better understanding of how immune cells in the body normally recognize and suppress KSHV and the cancers it can cause and then to develop new ways of using vaccines made from parts of this virus to boost the ability of AIDS patients to fight off KSHV and prevent and treat the diseases it causes.

描述（由申请人提供）：我们项目的目标是开发针对最常见艾滋病恶性肿瘤的病毒病原体的疫苗策略，即使是在 CD4+ T 细胞计数低（通常是 HIV 感染者的特征）的不利免疫环境中。在本提案中，我们选择卡波西肉瘤 (KS) 相关疱疹病毒（KSHV 或 HHV8）作为我们的模型目标，卡波西肉瘤 (KS) 是 KS、原发性渗出性淋巴瘤和多中心卡斯尔曼病的病原体。具体来说，我们将从 KSHV 的基因产物中识别相关的 CD8+ T 细胞表位，并开发疫苗接种方案，以引发对这些表位特异的效应和记忆 CD8+ T 细胞。该项目有可能为弱势患者群体的疫苗接种或受影响个体的过继转移治疗提供相关目标，并为免疫功能低下患者的新型疫苗接种方法的有效性提供证据。该申请与 RFA 的目标高度相关，因此更适合大机遇征集而不是挑战拨款：它将提供扩大 Kedes 和 Bullock 实验室之间新生但已经富有成效的跨学科合作的机会，导致疫苗靶点的识别，一种新的模型系统，用于测试所选靶点的相关性以及正在研究的疫苗接种方法的有效性（可能验证它们对与免疫功能低下相关的多种恶性肿瘤和疾病状态的使用）个人），并随着计划的发展立即提供新的就业机会和更多的就业机会。 公共卫生相关性：艾滋病毒/艾滋病患者无法抵抗许多传染病，包括可能导致癌症的特定病毒。尽管美国和其他发达国家等相对富裕的国家提供了良好的艾滋病毒治疗，但艾滋病患者死亡中近三分之一是由于癌症，其中一半是由两种病毒之一引起的，即 EBV 和鲜为人知的病毒， KSHV。在我们提议的研究中，我们重点关注 KSHV，它会导致卡波西肉瘤，这是一种最常见的与艾滋病相关的癌症。我们希望更好地了解体内免疫细胞通常如何识别和抑制 KSHV 及其可能引起的癌症，然后开发使用由该病毒部分制成的疫苗的新方法，以提高艾滋病患者的能力对抗 KSHV 并预防和治疗其引起的疾病。