Strategies for Therapeutic Vaccination Against KSHV

KSHV 治疗性疫苗接种策略

• 批准号: 7943993
• 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 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7943993
• 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; 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 cell response; 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）：我们项目的目的是制定疫苗策略，这些疫苗策略将针对最常见的艾滋病恶性病毒病原体恶性肿瘤，即使在低CD4+ T细胞计数的不利免疫学环境中，通常表征了HIV感染的患者。在该提案中，我们选择了与Kaposi的肉瘤（KS）相关疱疹病毒（KSHV或HHV8）的模型，KS的病因学剂，一级积液淋巴瘤和多中心castleman病。具体而言，我们将从KSHV的基因产物中确定相关的CD8+ T细胞表位，并开发疫苗接种方案，这些方案将引起效应子和记忆CD8+ T细胞特有的这些表位。该项目有可能为弱势患者人群的疫苗接种或受苦的个体的过继转移治疗提供相关目标，并证明新型疫苗接种方法在免疫功能低下的患者中的疗效。该应用与RFA的目标高度相关，因此更适合于盛大的机会征集，而不是挑战授予：它将提供一个机会，扩大了凯德斯和Bullock实验室之间偏小但已经有成果的跨学科合作的机会与免疫功能低下的人相关的恶性肿瘤和疾病状态），随着计划的增长，立即提供新的就业机会。 公共卫生相关性：艾滋病毒/艾滋病患者无法与许多传染病作斗争，包括可能引起癌症的特定病毒。尽管在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疗法，但艾滋病患者死亡的几乎三分之一是由于癌症引起的，其中一半是由两种病毒之一，EBV和鲜为人知的病毒引起的。在我们提出的研究中，我们将重点放在KSHV上，KSHV导致Kaposi的肉瘤是最常见的艾滋病相关癌症。我们希望能够更好地了解体内的免疫细胞通常识别和抑制KSHV及其可能引起的癌症，然后开发使用该病毒部分疫苗的新方法，以提高艾滋病患者抗击KSHV并预防和治疗其疾病的能力。