The Effect of HIV Infection on Malaria Specific T and B Cell Responses

HIV 感染对疟疾特异性 T 和 B 细胞反应的影响

• 批准号: 8644446
• 负责人: Anne Elizabeth Parker Frosch
• 金额: $ 5.83万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2015-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8644446
• 关键词: Address; Adult; Affect; Africa South of the Sahara; Antibodies; Antibody Formation; Antigens; Attenuated; B-Lymphocyte Subsets; B-Lymphocytes; Biological Assay; Blood; Blood specimen; Cell Count; Cells; Defect; Development; Disease; Falciparum Malaria; Flow Cytometry; Frequencies; Future; Goals; HIV; HIV Infections; HIV Seropositivity; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunoassay; Individual; Infection; Intervention; Kenya; Life; Literature; Maintenance; Malaria; Malaria Vaccines; Malaria prevention; Measures; Memory B-Lymphocyte; Morbidity - disease rate; Outcome; Outcomes Research; Participant; Persons; Plasmodium falciparum; Population; Predisposition; Proteins; Public Health; Research; Research Design; Role; Serological; Severities; T-Lymphocyte; Testing; Time; Tissues; Vaccine Design; Work; antiretroviral therapy; base; cell type; design; evidence base; exhaust; mortality; novel; public health relevance; response; treatment strategy; vaccine development

DESCRIPTION (provided by applicant): HIV infection has been demonstrated to increase vulnerability to malaria infection and disease, but the mechanisms behind this observation are not understood. Current evidence suggests that increased malaria vulnerability among individuals with HIV infection may be due in part to a defect in the immune system's ability to create and maintain antibodies that target malaria. This evidence includes a robust body of literature supporting the critical role of antibodies in protection from malaria and an increasing understanding of how HIV infection affects the immune systems ability to mount effective antibody responses. Specific Aims: 1) Determine antibody reactivity of HIV-positive versus HIV-negative individuals to multiple malaria proteins; 2) Determine the frequency of different types of B-cells that specifically target malaria. B cells are the immune cells responsible for antibody production, and different types of B cells have differing abilities to produce effective antibody responses. Study Design: For this study, blood will be collected from HIV infected and uninfected persons living in a malaria endemic region in Kenya. Antibody responses that target malaria and B cell numbers and types that target malaria will be measured in these blood samples and these responses will be compared between HIV infected and uninfected study participants. Potential Impact: This project will for the first time characterize malaria-specific -cell responses in HIV-positive individuals. It will assist in determining if this population should receive targeted malaria interventions and will help devise evidence-based strategies for malaria vaccine design and HIV treatment for HIV-positive individuals.

描述（由申请人提供）：已证明艾滋病毒感染会增加对疟疾感染和疾病的脆弱性，但这一观察结果背后的机制尚不清楚。目前的证据表明，艾滋病毒感染者感染疟疾的可能性增加，部分原因可能是免疫系统产生和维持针对疟疾的抗体的能力存在缺陷。这些证据包括大量文献支持抗体在预防疟疾方面的关键作用，以及对艾滋病毒感染如何影响免疫系统产生有效抗体反应的能力的日益了解。具体目标：1）确定HIV阳性与HIV阴性个体对多种疟疾蛋白的抗体反应性; 2）确定不同类型的疟疾的频率， 专门针对疟疾的B细胞。B细胞是负责抗体产生的免疫细胞，不同类型的B细胞具有不同的产生有效抗体应答的能力。研究设计：对于本研究，将从生活在肯尼亚疟疾流行区的HIV感染者和未感染者中采集血液。将在这些血液样本中测量靶向疟疾的抗体应答和靶向疟疾的B细胞数量和类型，并将这些应答在HIV感染和未感染的研究参与者之间进行比较。潜在影响：该项目将首次描述艾滋病毒阳性个体的疟疾特异性细胞反应。它将有助于确定这些人口是否应该 艾滋病毒/艾滋病规划署还将提供有针对性的疟疾干预措施，并将帮助制定疟疾疫苗设计和艾滋病毒抗体阳性者艾滋病毒治疗的循证战略。