The major challenge facing Pfs25-based TBV development is to find a formulation with great safety profile and capable of inducing sustained high antibody responses. Previously the LMIV has demonstrated that conjugating Pfs25 with carrier protein ExoProtein A (EPA) of Psuedomonas aeruginosa greatly enhance the immunogenicity of the recombinant Pfs25 produced in Pichia pastoris. A process was developed to conjugate Pfs25 with rEPA, and cGMP-grade Pfs25-EPA conjugate was manufactured and formulated with Alhydrogel. A Phase 1 trial was conducted in US. After demonstrating that vaccine was safe, immunogenic, and could induce transmission reducing activity, LMIV began a Phase 1 trial in Mali, to evaluate the vaccine safety, immunogenicity, and transmission blocking activity in target population.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$3,362,281
Indirect Cost
City
State
Country
Zip Code
Eastman, Richard T; Pattaradilokrat, Sittiporn; Raj, Dipak K et al. (2013) A class of tricyclic compounds blocking malaria parasite oocyst development and transmission. Antimicrob Agents Chemother 57:425-35
Da, Dari F; Dixit, Saurabh; Sattabonkot, Jetsumon et al. (2013) Anti-Pfs25 human plasma reduces transmission of Plasmodium falciparum isolates that have diverse genetic backgrounds. Infect Immun 81:1984-9
Shimp Jr, Richard L; Rowe, Christopher; Reiter, Karine et al. (2013) Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle. Vaccine 31:2954-62
Zhu, Daming; Qian, Feng; Wu, Yimin et al. (2013) Determination of protein concentration for protein-protein conjugates using ultraviolet absorption. J Immunol Methods 387:317-21