Defining targets of protective immunity to vivax malaria using human monoclonal antibodies

使用人单克隆抗体确定间日疟疾的保护性免疫目标

• 批准号: 10353401
• 负责人: Christopher L King
• 金额: $ 70.67万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-24 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10353401
• 关键词: Address; Adjuvant; Adult; Affinity; Africa South of the Sahara; Amino Acid Sequence; Antibodies; Antigens; Area; B-Lymphocytes; Binding Proteins; Biological Assay; Biomass; Blood; Brazil; Cambodia; Cells; Cessation of life; Child; Chimeric Proteins; Chronic; Clinical; Clone Cells; Complement; Copy Number Polymorphism; Data; Development; Drug resistance; Epitopes; Erythrocytes; Ethiopia; Event; Exposure to; Fever; Gene Dosage; Genetic Polymorphism; Geography; Goals; Health Policy; Hepatic; Hepatocyte; Human; Immune; Immune Sera; Immunity; Immunize; Immunoglobulin G; Immunologist; In Vitro; Individual; Infection; Infection prevention; Injections; Knowledge; Liver; Longitudinal cohort; Lymphocyte; Malaria; Malaria Vaccines; Measures; Mediating; Monoclonal Antibodies; Morbidity - disease rate; Papua New Guinea; Parasites; Patients; Persons; Plasmodium falciparum; Plasmodium vivax; Plasmodium vivax vaccine; Play; Population; Population Heterogeneity; Prevention; Prevention approach; Primary Infection; Production; Proteins; Public Health; Relapse; Residual state; Reticulocytes; Risk; Role; Solomon Islands; Sporozoites; Syndrome; Technology; Time; Transcend; Transgenic Organisms; Vaccines; Vivax Malaria; Work; apical membrane; circumsporozoite protein; design; disorder risk; experimental study; human monoclonal antibodies; in vitro Assay; in vivo; innovation; migration; mouse model; neutralizing monoclonal antibodies; next generation; novel strategies; novel therapeutics; novel vaccines; parasite invasion; prevent; rational design; receptor; receptor binding; sample fixation; transmission process; vaccine development; vaccine strategy; vaccine-induced immunity

The goal of our proposal is to develop new approaches for the prevention and treatment of human malaria caused by the parasite Plasmodium vivax (P. vivax). This type of malaria, known as vivax malaria, is the most widely distributed type of malaria with 3.3 billion people at risk and at least 15 million clinical cases worldwide each year. As the most common form of malaria outside sub-Saharan Africa, it can cause severe illness and death across a large segment of the world's population. Most individuals exposed to P. vivax through repeated infection gain partial immunity over time. The immunity is mediated, in part, by acquired antibodies (Abs) to essential parasite proteins that can block the parasite invasion into liver and red blood cells thereby preventing infection and if infected reduce the risk of disease. This proposal aims to isolate human monoclonal antibodies (mAbs) from individuals with immunity to vivax malaria that recognize a few key molecules known to be essential for invasion of liver and red blood cells. Once isolated these mAbs will be evaluated as to whether they block parasite invasion of liver and red cells in vitro, and in vivo using murine models and genetically modified parasites. Monoclonal Abs with potent blocking activity will be further characterized as to exactly how and where they interact with parasite proteins and whether individuals in diverse populations also have the same or similar antibodies. This information can be used to help to design a vaccine against vivax malaria. These mAbs can also be used for treatment of severely ill patients, or for prevention of vivax malaria over time, since a single injection of modified mAbs can last for weeks and even months.

我们建议的目标是开发预防和治疗人类疟疾的新方法