NOVEL LINEAR PEPTIDE UNIVERSALL MALARIA VACCINES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Clinical trials of synthetic peptide vaccines have indicated that biological adjuvants are required to induce a sustained immunity. Although several strategies have been used to optimize the delivery of peptide antigens, the data available show that an optimal formulation is not yet available. We recently reported a novel system to deliver subunit vaccines based in peptide constructs. The strategy includes the association of malaria universal T cell epitopes described by us and synthesized in tandem with B cell epitopes. Amino and carboxyl terminal cysteine residues were included in the linear sequences to increase subunit valence. We have confirmed that this topology favors the spontaneous polymerization of such linear peptide chimeras (LPCs) using SELDI mass spectroscopy, and that the immunogenicity of the peptide constructs depend on the presence of universal T cell epitopes and homo polymerization. These LPCs induced high antibody titers, cytokine production and long-lasting immune responses. This technological approach for antigen delivery has been advanced further, with the design and testing of an additional set of LPC immunogens, which elicited high affinity antibodies as well as Th1 and Th2 immune responses in different strains of mice. Complex LPCs containing up to three epitopes, which include a CTL-class I restricted nonamer, induce immune response against individual components. The successful delivery of CTL epitopes to the MHC class I compartment opens the possibility of using LPCs containing universal T cell epitopes for developing vaccines against intracellular pathogens as well as for induction of anti-tumoral immunity.