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

被引：35
作者：
Nganou-Makamdop, Krystelle [1 ]
van Roosmalen, Maarten L. [2 ]
Audouy, Sandrine A. L. [3 ]
van Gemert, Geert-Jan [1 ]
Leenhouts, Kees [2 ]
Hermsen, Cornelus C. [1 ]
Sauerwein, Robert W. [1 ]
机构：
[1] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands
[2] Mucosis BV, Groningen, Netherlands
[3] BiOMaDe Technol Fdn, Groningen, Netherlands
来源：
MALARIA JOURNAL | 2012年 / 11卷
关键词：
BLP; CSP; Delivery platform; Immunization; Malaria; Plasmodium berghei; PRIME-BOOST IMMUNIZATION; CELL IMMUNE-RESPONSE; C-TERMINAL FRAGMENT; LACTOCOCCUS-LACTIS; GEM PARTICLES; T-CELLS; IRRADIATED SPOROZOITES; SYNTHETIC POLYPEPTIDE; VACCINE DEVELOPMENT; MURINE MALARIA;
D O I：
10.1186/1475-2875-11-50
中图分类号：
R51 [传染病];
学科分类号：
100401 ;
摘要：
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 I Gamma N-gamma 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-gamma 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-gamma 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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页数：11
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