Malaria Journal (Feb 2012)

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

  • Nganou-Makamdop Krystelle,
  • van Roosmalen Maarten L,
  • Audouy Sandrine AL,
  • van Gemert Geert-Jan,
  • Leenhouts Kees,
  • Hermsen Cornelus C,
  • Sauerwein Robert W

DOI
https://doi.org/10.1186/1475-2875-11-50
Journal volume & issue
Vol. 11, no. 1
p. 50

Abstract

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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. Conclusion 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.

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