Synthetic LbL microparticle vaccines containing the conserved T1BT* epitope of Plasmodium falciparum elicit protective antibody and cellular immune responses with minimal inflammation (166.11)

Abstract

Microparticle vaccines containing the conserved T1B repeat and T* epitopes from the P. falciparum CS protein were synthesized via layer-by-layer (LbL) fabrication on a solid core; microcapsules were prepared by dissolution of the particle core. Mice immunized with microparticles or microcapsules yielded T1B-specific antibody responses that neutralized Plasmodium parasite in vitro. The mice also developed T1BT*-specific cellular responses, including Th1, Th2, and CD4+ cytotoxic effector cells. When challenged with PfPb, a recombinant P. bergheii expressing the T1B repeats from P. falciparum, 70-80% of the mice immunized with microparticle, and 40-50% immunized with microcapsule, showed >90% reduction in liver parasite burden compared to naïve challenged mice. A minority of mice with reduced parasite burden did not have potent PfPb-neutralizing antibody activity. Since depletion of either CD4+ or CD8+ cells prior to challenge did not ablate protection, the vaccine-induced protection appears to be primarily associated with antibody responses but may also involve other mechanisms not yet defined. An examination of cytokine and chemokine gene expression in the liver post-challenge did not reveal any evidence of inflammatory responses following LbL vaccination and PfPb challenge. These results demonstrate that synthetic LbL vaccines bearing the conserved T1BT* epitopes can elicit protective immunity against Plasmodium without triggering unwanted inflammatory responses.