Malaria Vaccines: Pfs25-Pfs25/ALHYDROGEL

虽然Pfs25已被证明可以诱导抗体，阻止蚊子体内寄生虫的发育，但这种蛋白质的免疫原性很差。因此，基于pfs25的TBV开发面临的主要挑战是提高免疫原性和应答时间。免疫学家很早就知道，化学交联不良蛋白质免疫原本身会增加其免疫原性。在与博士合作。来自NICHD发育和分子免疫学实验室的John Robbins和Rachel Schneerson，我们正在开发一种由Pfs25-Pfs25偶联物组成的结合疫苗。各种偶联化学和方法被评估为最高的免疫原性和稳健的偶联过程。对Pfs25-Pfs25的生物化学特性进行了表征，并对其偶联物进行了动物免疫原性评价。对结合疫苗诱导的免疫血清在蚊子体内阻断寄生虫发育的能力进行了测试。一项1期试验计划用于测试安全性、免疫原性和在人体中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.