title: Bacterium-like particles as multi-epitope delivery platform for Plasmodium berghei circumsporozoite protein induce complete protection against malaria in mice.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Krystelle
authors.initials: K
authors.lastname: Nganou-Makamdop
authors.forename: Maarten L
authors.initials: ML
authors.lastname: van Roosmalen
authors.forename: Sandrine A L
authors.initials: SA
authors.lastname: Audouy
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: van Gemert
authors.forename: Kees
authors.initials: K
authors.lastname: Leenhouts
authors.forename: Cornelus C
authors.initials: CC
authors.lastname: Hermsen
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics; D000939:Epitopes / Q000276:immunology*; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
chemical_list: D000939:Epitopes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan