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 P...

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Bibliographic Details
Published in:Malaria Journal
Main Authors: Nganou-Makamdop Krystelle, van Roosmalen Maarten L, Audouy Sandrine AL, van Gemert Geert-Jan, Leenhouts Kees, Hermsen Cornelus C, Sauerwein Robert W
Format: Article in Journal/Newspaper
Language:English
Published: BMC 2012
Subjects:
BLP
CSP
Delivery platform
Immunization
Malaria
Plasmodium berghei
Arctic medicine. Tropical medicine
RC955-962
Infectious and parasitic diseases
RC109-216
Arctic
Online Access:https://doi.org/10.1186/1475-2875-11-50
https://doaj.org/article/baa76770997d47e3ae28563d9ac3a81d
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Summary: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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