Malaria Vaccines: Pfs25-Pfs25/ALHYDROGEL

尽管Pfs25已经被证明可以诱导抗体来阻止蚊子体内寄生虫的发展，但这种蛋白的免疫原性很差。因此，基于Pfs25的TBV开发面临的主要挑战是提高免疫原性和反应寿命。免疫学家很久以前就知道，化学交联剂将劣质的蛋白质免疫原与自身进行交联会增强其免疫原性。与NICHD发育和分子免疫学实验室的John Robbins博士和Rachel Schneerson博士合作，我们正在开发一种由Pfs25-Pfs25结合物组成的结合疫苗。为了获得最高的免疫原性和可靠的接合过程，对各种接合化学方法和方法进行了评估。对Pfs25-Pfs25的生化性质进行了表征，并对其免疫原性进行了动物实验。结合疫苗诱导的免疫血清被测试其阻止蚊子寄生虫发展的能力。已计划进行一项第一阶段试验，以测试其安全性、免疫原性和在人体内的体外传播阻断活性。

Though Pfs25 has been shown to induce antibodies that can block parasite development in mosquitoes, the protein is poorly immunogenic. Thus the major challenge facing Pfs25-based TBV development is to increase the immunogenicity and response longevity. Immunologists have know for long time that chemical cross-linking a poor protein immunogen to itself would increase its immunogenicity. In collaboration with Drs. John Robbins and Rachel Schneerson at the Laboratory of Developmental and Molecular Immunology of the NICHD, we are developing a conjugate vaccine consists of Pfs25-Pfs25 conjugates. Various conjugation chemistries and methods were evaluated for the highiest immunogenicity and the robust conjugation processes. The biochemical properties of the Pfs25-Pfs25 were characterized and the conjugates were evaluated in animals for their immunogenicity. The immune sera induced by the conjugate vaccine were tested for their ability to block parasite development in mosquitoes. A Phase 1 trial has been planned to test the safety, immunogenicity, and ex vivo transmission blocking activity in humans.