PLASMODIUM VIVAX MSP-3 AND MSP-9 AS VACCINE IMMUNOGENES

间日疟原虫 MSP-3 和 MSP-9 作为疫苗免疫原

• 批准号: 7057851
• 负责人: MARY R GALINSKI
• 金额: $ 38.76万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7057851
• 关键词: B lymphocyte; Ceboidea; Macaca mulatta; Plasmodium; T lymphocyte; biotechnology; clinical research; enzyme linked immunosorbent assay; epitope mapping; gene induction /repression; human tissue; immune response; laboratory mouse; laboratory rabbit; malaria vaccines; recombinant proteins; species difference; surface antigens; vaccine development; vaccine evaluation; vector vaccine

DESCRIPTION (provided by applicant): The broad long-term objective of this project is to develop Plasmodium vivax merozoite surface protein-3 (PvMSP-3) and PvMSP-9 recombinant proteins as candidate malaria vaccine products. This laboratory originally identified, expressed, and characterized these proteins and their potential as malaria vaccine candidates. The specific aims of the proposed studies are to: 1) Optimize the expression of PvMSP-3 and PvMSP-9 full-length and partial gene constructs in bacterial or yeast expression systems to obtain appropriate products for further testing of these antigens as malaria vaccine candidates; 2) Identify natural immunogenic B and T cell epitopes in PvMSP-3 and PvMSP-9 by evaluating currently available blood samples from individuals with different levels of exposure to P. vivax malaria infections in endemic areas of Brazil; 3) Evaluate immune responses in mice and rabbits, generated against several PvMSP-3 and PvMSP-9 candidate vaccine containing B and T cell epitopes formulated in clinical grade adjuvants; and 4) Test the safety, immunogenicity and efficacy of selected PvMSP-3 and PvMSP-9 candidate vaccine formulations in non-human primates. This research aims to produce up to three candidate products that can be evaluated for vaccine efficacy in New World monkeys. These primates are susceptible to P. vivax infections and can serve very well as a direct challenge model. The most promising products will also be tested in rhesus macaques for safety and immunogenicity in order to judge the potential for producing adequate responses in human clinical studies. Importantly, challenge with P. cynomolgi blood-stage parasites (the malaria species most closely related to P. vivax) will also be carried out in these immunized animals to determine if cross-species protection could be achieved. If warranted, to maximize the potential to evaluate protection in this model, the P. cynomolgi counterpart immunogens may also be produced and tested for efficacy and the ability of secondary infections to boost functional immunity in macaques. These combined approaches will help to identify the most efficacious PvMSP-3 and PvMSP-9 vaccine immunogens. This proposal will advance the development of several P. vivax vaccine candidates based on these antigens and also serve to establish reliable procedures to test and evaluate antigens in non-human primate models for safety, immunogenicity and efficacy.

描述（由申请人提供）：该项目的广泛长期目标是开发Vivax Merozoite表面蛋白3（PVMSP-3）和PVMSP-9重组蛋白作为候选疟疾疫苗产品。该实验室最初鉴定出，表达和表征这些蛋白质及其潜力是疟疾疫苗候选物。拟议研究的具体目的是：1）优化细菌或酵母表达系统中PVMSP-3和PVMSP-9的全长和部分基因构建体的表达，以获取适当的产物，以进一步测试这些抗原作为疟疾疫苗的候选者; 2）通过评估来自巴西流行地区的流域不同程度的流失于Vivax疟疾感染的个体的当前可用的血液样本，从而确定PVMSP-3和PVMSP-9中的天然免疫原性B和T细胞表位； 3）评估小鼠和兔子中的免疫反应，对几种PVMSP-3和PVMSP-9候选疫苗产生，其中含有B和T细胞表位，这些疫苗在临床级辅助剂中配制了B和T细胞表位； 4）测试非人类灵长类动物中选定的PVMSP-3和PVMSP-9候选疫苗配方的安全性，免疫原性和功效。这项研究旨在生产多达三种可以评估新世界猴子疫苗功效的候选产品。这些灵长类动物容易受到疟原虫感染的影响，并且可以很好地作为直接挑战模型。最有希望的产品还将在恒河猕猴中进行安全性和免疫原性测试，以判断人类临床研究中产生适当反应的潜力。重要的是，P. cynomolgi血液阶段的挑战 在这些免疫动物中也将进行寄生虫（与疟原虫最密切相关的疟疾物种），以确定是否可以实现跨物种保护。如果有必要在此模型中最大程度地评估保护的潜力，也可以生产并测试cynomolgi P. cynomolgi的免疫原子，并测试疗效以及继发性感染提高猕猴中功能免疫力的能力。这些组合方法将有助于鉴定最有效的PVMSP-3和PVMSP-9疫苗免疫原。该提案将基于这些抗原的几种候选疫苗的候选者的发展，还可以建立可靠的程序来测试和评估非人类的抗原 灵长类动物模型的安全性，免疫原性和功效。