Immunogenicity and structural characterisation of an in vitro folded meningococcal siderophore receptor (FrpB, FetA)

被引:20
作者
Kortekaas, Jeroen
Mueller, Shirley A.
Ringler, Philippe
Gregorini, Marco
Weynants, Vincent E.
Rutten, Lucy
Bos, Martine P.
Tommassen, Jan
机构
[1] Univ Utrecht, Dept Mol Microbiol, Biomembrane Inst, NL-3584 CH Utrecht, Netherlands
[2] Univ Basel, Bioctr, Maurice E Muller Inst Struct Biol, CH-4056 Basel, Switzerland
[3] GlaxoSmithKline Biol, B-1330 Rixensart, Belgium
[4] Univ Utrecht, Dept Crystal & Struct Chem, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands
关键词
in vitro folding; Neisseria meningitidis; outer membrane protein; vaccine;
D O I
10.1016/j.micinf.2006.04.011
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The iron-limitation-inducible protein FrpB of Neisseria meningitidis is an outer-membrane-local i zed siderophore receptor. Because of its abundance and its capacity to elicit bactericidal antibodies, it is considered a vaccine candidate. Bactericidal antibodies against FrpB are, however, type-specific. Hence, an FrpB-based vaccine should comprise several FrpB variants to be capable of providing broad protection. To facilitate the development of a meningococcal subunit vaccine, we have established a procedure to obtain large quantities of the protein in a native-like conformation. The protein was expressed without its signal sequence in Escherichia coli, where it accumulated in inclusion bodies. After in vitro folding, the protein was biochemically, biophysically and biologically characterised. Our results show that in vitro folded FrpB assembles into oligomers, presumably dimers, and that it induces high levels of bactericidal antibodies in laboratory animals. (c) 2006 Elsevier SAS. All rights reserved.
引用
收藏
页码:2145 / 2153
页数:9
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