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. OMPC, the Outer Membrane Protein Complex of the Neisseria meningitides subgroup B, has been used as a carrier in commercially licensed polysaccharide vaccines to increase polysaccharide immunogenicity. In collaboration with Merck Research Laboratories, we have developed a process to conjugated Pfs25 with OMPC. The immunogenicity and the response longevity of the Pfs25-OMPC conjugate was evaluated in mice, rabbits, and rhesus monkeys. The conjugates transmission blocking activity was evaluated in an ex-vivo membrane feeding assay. Multiple conjugate batches were produced and evaluated to demonstrate the robustness of the conjugation process.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2009
Total Cost
$112,078
Indirect Cost
City
State
Country
Zip Code
An, So Jung; Scaria, Puthupparampil V; Chen, Beth et al. (2018) Development of a bivalent conjugate vaccine candidate against malaria transmission and typhoid fever. Vaccine 36:2978-2984
Radtke, Andrea J; Anderson, Charles F; Riteau, Nicolas et al. (2017) Adjuvant and carrier protein-dependent T-cell priming promotes a robust antibody response against the Plasmodium falciparum Pfs25 vaccine candidate. Sci Rep 7:40312
Scaria, Puthupparampil V; Chen, Beth; Rowe, Christopher G et al. (2017) Protein-protein conjugate nanoparticles for malaria antigen delivery and enhanced immunogenicity. PLoS One 12:e0190312
Jones, David S; Rowe, Christopher G; Chen, Beth et al. (2016) A Method for Producing Protein Nanoparticles with Applications in Vaccines. PLoS One 11:e0138761
MacDonald, Nicholas J; Nguyen, Vu; Shimp, Richard et al. (2016) Structural and Immunological Characterization of Recombinant 6-Cysteine Domains of the Plasmodium falciparum Sexual Stage Protein Pfs230. J Biol Chem 291:19913-22
Wu, Yimin; Sinden, Robert E; Churcher, Thomas S et al. (2015) Development of malaria transmission-blocking vaccines: from concept to product. Adv Parasitol 89:109-52
Cheru, Lediya; Wu, Yimin; Diouf, Ababacar et al. (2010) The IC(50) of anti-Pfs25 antibody in membrane-feeding assay varies among species. Vaccine 28:4423-9
Kubler-Kielb, Joanna; Majadly, Fathy; Biesova, Zuzana et al. (2010) A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates. Proc Natl Acad Sci U S A 107:1172-7