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. An on-going study is aimed at evaluating activation of memory B-cells by the conjugate vaccine, and whether the antibody responses induced by the conjugates are sustained over the time.
| 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 |
