Development of Pre-Erythrocytic Malaria Vaccines

前红细胞疟疾疫苗的开发

• 批准号: 8946601
• 负责人: ROBERT A SEDER
• 金额: $ 52.45万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8946601
• 关键词: Adjuvant; Antibodies; Area; Attenuated; Biological Assay; Bite; Blood; CD4 Positive T Lymphocytes; Clinical Trials; Culicidae; Development; Dose; Drug Formulations; Erythrocytes; Goals; Heterogeneity; Human; Immune; Immunity; Immunization; Immunologic Adjuvants; Infection; Liver; Malaria; Malaria Vaccines; Modeling; Monoclonal Antibodies; Mus; Phase; Phase I Clinical Trials; Preventive; Proteins; Radiation; Regimen; Route; Sampling; Schedule; Spleen; Sporozoite vaccine; Sporozoites; T cell response; T-Lymphocyte; Therapeutic; Vaccinated; Vaccination; Vaccines; Viral Vector; circumsporozoite protein; immunogenicity; insight; response

The major discovery this year are as follows. 1. Initiated a phase I clinical trial assessing whether irradiated PfSPZ given by the IV or IM route is safe, and confers durable immunity and protection using various doses and intervals for immunization. 2. Characterized the sporozoite specific T cell and NK responses longitudinally following vaccination and infection to provide insights into the correlates of protection. Used Fluidigm to characterize the heterogeneity of the sporozoite specific CD4+ T cell response in vaccinated/protected versus vaccinated/unprotected or control infected subjects. 3. Isolated monoclonal antibodies against malaria specific proteins ( eg CSP) in vaccinated and protected subjects.

今年的主要发现如下。 1.启动了一项I期临床试验，评估通过静脉或肌注途径给予的辐照PfSPZ是否安全，并使用不同的免疫剂量和间隔提供持久的免疫和保护。 2.对接种和感染后的子孢子特异性T细胞和NK细胞的纵向反应进行表征，以提供对保护相关因素的深入了解。使用Fluidigm来表征接种/保护与接种/未保护或对照感染受试者中子孢子特异性CD4+T细胞反应的异质性。 3.在疫苗接种和保护对象中分离出抗疟疾特异性蛋白(如CSP)的单抗。