MAPPING AND IMMUNE REFOCUSING ANTIBODY RESPONSE IN MSP1

MSP1 中抗体反应的绘制和免疫重新聚焦

• 批准号: 2869401
• 负责人: PETER Lloyd NARA
• 金额: $ 10万
• 依托单位: BIOLOGICAL MIMETICS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-15 至 1999-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2869401
• 关键词: Escherichia coli; Plasmodium falciparum; blocking antibody; conformation; enzyme linked immunosorbent assay; epitope mapping; malaria vaccines; monoclonal antibody; protozoal antigen; vaccine development

DESCRIPTION (Adapted from the Applicant's Abstract): One of the most difficult obstacles faced in the development of a malaria vaccine is to overcome the ability of the parasite to misdirect immune responses away from the critical protective epitopes. Overcoming problems associated with misdirected immune responses and antigenic diversity may be extremely important in making a malaria vaccine possible. Clinical symptoms of malaria are associated with asexual multiplication of merozoites within erythrocytes. Unlike sporozoite based vaccines which render the host infection free, the goal of a merozoite vaccine is to render patients clinically asymptomatic. The long term objective of this proposal is to develop and commercialize an erythrocyte stage MSP1-42 malaria vaccine against P. falciparum. The malaria merozoite protein MSP-1 is proteolytically cleaved to MSP-33 and MSP-19. The immune response to tp MSP-1 in mice and humans elicits both protective (proteolytic inhibiting-Iab) and parasite enhancing (blocking antibodies-Babs). Babs interfere with the with the protective immunity of Iabs through stearic hindrance on the MSP1 protein. This study proposes to enhance the protective efficacy of a MSP-1 as a vaccine by turning down the immune responses to the protective Iab domain. Phase I will involve mapping the immune dampening of Bab epitopes on MSP1-42. Modified recombinant proteins will be expressed in E. coli and tested for the loss of Bab binding while still retaining the ability to bind Iabs. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（改编自申请人的摘要）： 在研制疟疾疫苗方面所面临的障碍是克服 寄生虫有能力误导免疫反应，使其偏离关键部位 保护性表位克服与错误定向免疫相关的问题 免疫应答和抗原多样性可能在制造免疫应答中极其重要。 疟疾疫苗的可能性疟疾的临床症状与 裂殖子在红细胞内的无性繁殖。与子孢子不同 基于疫苗，使宿主感染免费，裂殖子的目标， 疫苗是使患者临床上无症状。长期目标 该提案的一个重要目的是开发和商业化红细胞阶段MSP 1 -42 针对恶性疟原虫的疟疾疫苗。疟疾裂殖子蛋白MSP-1是 蛋白水解裂解为MSP-33和MSP-19。对tp MSP-1的免疫应答 在小鼠和人类中， 寄生虫增强（阻断抗体-Babs）。巴布斯干扰了 Iabs通过对MSP 1蛋白的空间位阻而产生保护性免疫。这 一项研究提出，通过以下方式增强MSP-1作为疫苗的保护效力： 降低对保护性Iab结构域的免疫应答。一期将 涉及MSP 1 -42上Bab表位的免疫抑制作图。改性 重组蛋白将在E.大肠杆菌，并测试了损失 Bab结合，同时仍保留结合Iabs的能力。 拟议商业应用：不可用