Malaria Vaccine: Pfs25-OMPC/MERCK ALUMINUM ADJUVANT

虽然Pfs 25已被证明可以诱导抗体，可以阻止蚊子体内的寄生虫发育，但这种蛋白质的免疫原性很差。 因此，基于Pfs 25的TBV开发面临的主要挑战是增加免疫原性和应答寿命。 OMPC，脑膜炎奈瑟氏菌亚群B的外膜蛋白复合物，已在商业许可的多糖疫苗中用作载体以增加多糖免疫原性。 与默克研究实验室合作，我们开发了一种将Pfs 25与OMPC结合的方法。 在小鼠、兔和恒河猴中评价Pfs 25-OMPC缀合物的免疫原性和应答寿命。 在离体膜进食测定中评价缀合物的传递阻断活性。 生产并评价了多个结合物批次，以证明结合工艺的耐用性。

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.