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 the US that 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 immunogenicity and response longevity. ExoProtein A (EPA) has been used as a carrier for the Vi polysaccharide vaccine against typhoid fever. We have produced recombinant EPA (rEPA), and developed a process to conjugate Pfs25 with rEPA. Various conjugation chemistries and methods were evaluated for optimal immunogenicity and a robust conjugation processes. The biochemical properties of 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 safety, immunogenicity, and ex-vivo transmission blocking activity in humans.
