A Plasmodium falciparum GLURP-MSP3 chimeric protein;: expression in Lactococcus lactis, immunogenicity and induction of biologically active antibodies

被引:78
作者
Theisen, M [1 ]
Soe, S
Brunstedt, K
Follmann, F
Bredmose, L
Israelsen, H
Madsen, SM
Druilhe, P
机构
[1] State Serum Inst, Dept Clin Biochem, Copenhagen, Denmark
[2] Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen, Denmark
[3] Inst Pasteur, Lab Parasitol Med, Paris, France
[4] Inst Biotechnol, Dept Lact Acid Bacteria, Horsholm, Denmark
关键词
Plasmodium falciparum; immunogenicity; antibodies; Lactococcus expression;
D O I
10.1016/j.vaccine.2003.09.017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Plasmodium falciparum malaria is a major cause of morbidity and mortality worldwide. To evaluate the efficacy of a possible vaccine antigen against P. falciparum infection, a fusion protein, derived from P falciparum Glutamate-rich protein (GLURP) genetically coupled to P falciparum Merozoite surface protein 3 (MSP3) was produced in Lactococcus lactis as a secreted recombinant GLURP-MSP3 fusion protein. The hybrid protein was purified to homogeneity by ion exchange and hydrophobic-interaction chromatography and its composition was verified by MALDI MS, SDS/PAGE and Western blotting with antibodies against antigenic components of GLURP and MSP3. Mice immunized with the hybrid protein produced higher levels of both GLURP- and MSP3-specific antibodies than mice immunized with either GLURP, MSP3 or a mix of both. The protective potential of the hybrid protein was also demonstrated by in vitro parasite-growth inhibition of mouse anti-GLURP-MSP3 IgG antibodies in a monocyte-dependent manner. These results indicate that the GLURP-MSP3 hybrid could be a valuable strategy for future P falciparum vaccine development. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1188 / 1198
页数:11
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