Malaria Vaccines: TBV Antigens as Conjugates with Alternate Carriers

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

OMPC is a proprietary carrier from Merck Research Laboratories. In collaboration with Merck, we have demonstrated that conjugating Pfs25 with OMPC, the Outer Membrane Protein Complex of the Neisseria meningitides subgroup B, significantly increased immunogenicity and response longevity of Pfs25 in multiple animal models, including non-human primates. The induced immune sera effectively blocked malaria transmission as evaluated in an ex-vivo membrane feeding assay. Subsequently, the collaborative efforts continued to evaluate conjugates using different carriers and adjuvants, searching for a cost-effective process for vaccine product development, with the result that Pfs25 conjugated to the alternative carrier EPA was produced and further progress on that vaccine candidate is reported elsewhere. During the past year, LMIV and Merck have resumed this collaboration with the following goals: 1) transfer the OMPC conjugation methodologies from Merck to LMIV so that conjugates can be produced in house at LMIV; 2) reproduce the earlier findings in mice and primates showing strong durable antibody responses to the OMPC-Pfs25 conjugate; 3) prepare and assess OMPC-Pfs230 conjugates in a similar fashion. Based on the results of these small animal studies, we will determine whether to proceed to NHP studies to compare the OMPC conjugates to our EPA conjugates for immunogenicity and durability of functional antibody. Vi Polysaccharide conjugates of TBV antigens: Working in collaboration with International Vaccine Institute (IVI), Seoul S. Korea, we are working on developing conjugates of Pfs25 and Pfs230 antigens with Vi polysaccharide with the goal of developing it as a bivalent vaccine against Malaria and Typhoid fever. Vi polysaccharide is currently approved as a vaccine for Typhoid fever. Progress in this area is summarized in Scientific Advances section below. Additionally we continue to explore other protein carriers such as Tetanus toxoid, CRM197 as alternate carriers for TBV antigens.