Abstract
BackgroundVirus-like particles have been regularly used as an antigen delivery system for a number of Plasmodium peptides or proteins. The present study reports the immunogenicity and protective efficacy of bacterium-like particles (BLPs) generated from Lactococcus lactis and loaded with Plasmodium berghei circumsporozoite protein (PbCSP) peptides.MethodsA 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.ResultsBLP-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.ConclusionPresentation 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.
Highlights
Virus-like particles have been regularly used as an antigen delivery system for a number of Plasmodium peptides or proteins
Immune responses and protective efficacy were studied in a murine model following parenteral immunizations with Bacterium-like particle (BLP) carrying Plasmodium berghei circumsporozoite protein (PbCSP) peptides
BLP-PbCSP1 induces parasite-specific antibodies but no IFN-g response BLP-PbCSP1 was produced by expression of both CSP B- and T-cell epitopes in two different Protan fusion products (Figure 2A)
Summary
Virus-like particles have been regularly used as an antigen delivery system for a number of Plasmodium peptides or proteins. The present study reports the immunogenicity and protective efficacy of bacterium-like particles (BLPs) generated from Lactococcus lactis and loaded with Plasmodium berghei circumsporozoite protein (PbCSP) peptides. But non-covalent attachment of antigens to the surface of BLPs is mediated by using a lactococcal peptidoglycan binding domain called Protan [18]. The ability of Lactococcus lactis BLPs to elicit systemic antibodies against the Plasmodium falciparum merozoite surface antigen 2 was evaluated [23]. Immune responses and protective efficacy were studied in a murine model following parenteral immunizations with BLPs carrying Plasmodium berghei circumsporozoite protein (PbCSP) peptides
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