Malaria Vaccines: Pfs25-rEPA/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。一种油包水佐剂Montanide ISA 51能够增强Pfs25的免疫原性，然而，该配方的反应性太强，在美国进行的一项1期人体试验中，该配方必须在完成前终止。

Though Pfs25 has been shown to induce antibodies that can block parasite development in mosquitoes, the protein is poorly immunogenic. A water-in-oil adjuvant Montanide ISA 51 was able to enhance the immunogenicity of the Pfs25, however, the formulation was too reactogenic and a Phase 1 human trial in US tested the formulation had to be terminated before completion. Thus the major challenge facing Pfs25-based TBV development is to find a formulation to increase the immunogenicity and response longevity. The ExoProtein A (EPA) has been used as a carrier for the Vi polysaccharide vaccine against typhoid fever. We have produced the recombinant EPA (rEPA), and developed a process to to conjugate Pfs25 with rEPA. Various conjugation chemistries and methods were evaluated for the optimal 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.