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 commercially licensed polysaccharide vaccines to increase the immunogenicity of polysaccharide. 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 tranmission 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. A Phase 1 trial has been planned to test the safety, immunogenicity, and ex vivo transmission blocking activity in humans. The Phase 1 trial will use a recombinant Pfs25 without histidine tag.
| Wu, Yimin; Przysiecki, Craig; Flanagan, Elizabeth et al. (2006) Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex. Proc Natl Acad Sci U S A 103:18243-8 |
