Immunogenicity and Protection of the mXCL1-PyCSP Fusion Protein Prime-and-Trap DNA Vaccine in a Murine Malaria Immunization/Challenge Model

Abstract

Malaria is a life-threatening parasitic disease caused by Plasmodium spp. and is transmitted byfemale Anopheles spp. mosquitoes. Annually, there are nearly 250 million cases worldwide causing over 600,000 deaths, primarily in children under 5 years of age in sub-Saharan Africa. Currently, no highly efficacious (>85–90%) vaccine exists, hence the development of such a vaccine against human malaria infection is of paramount importance. The chemokine ligand XCL1, also known as lymphotactin, binds to its chemokine receptor XCR1. Recent studies have shown that XCL1-antigen fusion proteins efficiently induce CD8+ T cell responses by preferentially delivering antigens to cross-presenting dendritic cells expressing XCR1. In this study, we evaluated the immunogenicity of a fusion protein of the murine XCL1 chemokine and the Plasmodium yoelii circumsporozoite protein (mXCL1-PyCSP) in our “Prime-and-Trap” vaccine in a murine model of malaria. We hypothesized that this fusion protein vaccine would increase immunogenicity and protection outcomes compared to the standard unfused PyCSP vaccine. In summary, we showed that the fusion of PyCSP with the mXCL1 chemokine enhanced cell-mediated immune responses and significantly increased immunogenicity in male and female BALB/cJ mice, while not hampering protection outcomes in female mice. Fusion with mXCL1 may also reduce the need for cluster priming and improve vaccine scheduling. Overall, the data obtained in the present study could contribute to the overall goal of improving the efficacy of pre-erythrocytic malaria vaccines.