Bacterium-like particles as multi-epitope delivery platform for Plasmodium berghei circumsporozoite protein induce complete protection against malaria in mice

A panel of BLP-PbCSP formulations differing in composition and quantity of B-cell, CD4+ and CD8+ T-cell epitopes of PbCSP were tested in BALB/c mice.BLP-PbCSP1 induced specific humoral responses but no IFN-γ ELISPOT response, protecting 30-40% of the immunized mice. BLP-PbCSP2, with reduced length of the non-immunogenic part of the T-cell-epitopes construct, increased induction of IFN-γ responses as well as protection up to 60-70%. Compared to controls, lower parasitaemia was observed in unprotected mice immunized with BLP-PbCSP1 or 2, suggestive for partial immunity. Finally, further increase of the number of B-cell epitopes and codon optimization (BLP-PbCSP4) induced the highest anti-CSP antibody levels and number of IFN-γ spots, resulting in sterile immunity in 100% of the immunized mice.Presentation of Plasmodium-derived antigens using BLPs as a delivery system induced complete protection in a murine malaria model. Eventually, BLPs have the potential to be used as a novel versatile delivery platform in malaria vaccine development.By 2009, nearly a quarter of a billion people worldwide suffered from a malaria infection that resulted in approximately 800,000 deaths each year, mainly of children in sub-Saharan Africa [1]. Long-term solutions to stop deaths caused by malaria include the development of a prophylactic vaccine. Pre-erythrocytic stages of the parasite have been the principle target for vaccine development [2]. Effective delivery systems are required to optimize immune responses and protection by sub-unit based vaccines [3]. As such, virus-like particles (VLPs) have emerged as promising candidates able to induce cell-mediated immunity [4]. Due to its abundant presence on the sporozoite's surface [5], the circumsporozoite protein (CSP) has been the prime target for pre-erythrocytic protein-based malaria vaccine development [6-9]. In the Plasmodium berghei murine model, CSP immunizations with virally vectored delivery systems have been to shown to induce p