Malaria Vaccines: TBV Antigens as Conjugates with Alternate Carriers

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Evaluation of OMPC as a carrier: OMPC is a proprietary carrier from Merck Research Laboratories. In collaboration with Merck, we have previously demonstrated that conjugating Pfs25 with OMPC significantly increased immunogenicity and response longevity of Pfs25 in multiple animal models, including nonhuman primates. The induced immune sera effectively blocked malaria transmission as evaluated in an ex-vivo membrane feeding assay. During the past year, we have established synthesis of Pfs25-OMPC conjugates in house, and evaluated immune responses in mice. Based on these studies that showed enhanced immune response, we have started studies in nonhuman primates to evaluate the longevity of the antibody response from OMPC conjugates. In addition, we have synthesized Pfs230-OMPC conjugates and these are also being evaluated in mice and nonhuman primates for antibody responses and longevity. Evaluation of Vi Polysaccharide conjugates of TBV antigens: Working in collaboration with the International Vaccine Institute (IVI), Seoul S. Korea, we are developing conjugates of Pfs25 and Pfs230 antigens with Vi polysaccharide with the goal of producing a bivalent vaccine against malaria and typhoid fever. Vi polysaccharide is currently approved as a vaccine for Typhoid fever. We have synthesized a number of Vi conjugates of Pfs25 and Pfs230 and evaluated their immune response in mice. These studies showed antibody responses against the TBV antigens comparable to that obtained by EPA conjugates. Conjugation also resulted in increased antibody responses against the Vi polysaccharide, demonstrating its utility as a bivalent vaccine against malaria and typhoid. Currently, we are pursuing studies to optimize the conjugate synthesis and expand it to other malaria antigens including Plasmodium vivax antigens. Progress in this area is summarized in Scientific Advances section below. Evaluation of TThc and EcoCRM as carriers: In collaboration with FinaBio, we are currently evaluating two other carriers, TThc (Tetanus toxin heavy chain) and EcoCRM (a version of CRM197 expressed in E. Coli) as potential carriers. Current activities involve synthesizing conjugates of TThc and EcoCRM with TBV antigens and evaluating them in mouse immunogenicity studies to test their utility as carriers of TBV antigens and to examine how they compare with other carriers such as tetanus toxoid and CRM197. We have synthesized Pfs25 conjugates of TThc and EcoCRM and studied their immunogenicity in mice, and are currently working on synthesizing Pfs230 conjugates of TThc and EcoCRM.