Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component

被引:132
作者
Thompson, EAL
Feavers, IM
Maiden, MCJ
机构
[1] Univ Oxford, Dept Zool, Oxford OX1 3SY, England
[2] Natl Inst Biol Stand & Controls, S Mimms EN6 3QG, Herts, England
来源
MICROBIOLOGY-SGM | 2003年 / 149卷
关键词
D O I
10.1099/mic.0.26131-0
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Meningococcal FetA (FrpB), an iron-regulated outer-membrane protein and vaccine component, was shown to be highly diverse: a total of 60 tetA alleles, encoding 56 protein sequences, were identified from 107 representative Neisseria meningitidis isolates. Phylogenetic analysis established that the allelic variants had been generated by both point mutation and horizontal genetic exchange. Nucleotide substitution was unevenly distributed in the gene, which contained both conserved and variable sequence regions. The most conserved region of the translated peptide sequence corresponded to an amino-terminal domain of the protein and the most diverse region to a previously identified variable region (VIR). A nomenclature system for the peptides encoded by the VIR was devised which classified 24 variants into 5 FetA variant families. On the basis of these data, murine polyclonal sera specific for four FetA variants were generated. The reactivities of these sera in whole-cell ELISA experiments were consistent with the hypothesis that the VIR encoded an immunodominant epitope and indicated that the sera reacted mainly with variants against which they were raised. The diversity of this protein is likely to limit its effectiveness as a vaccine component.
引用
收藏
页码:1849 / 1858
页数:10
相关论文
共 51 条
[1]   VACCINE POTENTIAL OF MENINGOCOCCAL FRPB - STUDIES ON SURFACE EXPOSURE AND FUNCTIONAL ATTRIBUTES OF COMMON EPITOPES [J].
ALAALDEEN, DA ;
DAVIES, HA ;
BORRIELLO, SP .
VACCINE, 1994, 12 (06) :535-541
[2]   Split Decomposition: A New and Useful Approach to Phylogenetic Analysis of Distance Data [J].
Bandelt, Hans-Juergen ;
Dress, Andreas W. M. .
MOLECULAR PHYLOGENETICS AND EVOLUTION, 1992, 1 (03) :242-252
[3]   CLONING, SEQUENCING, AND CHARACTERIZATION OF THE GENE ENCODING FRPB, A MAJOR IRON-REGULATED, OUTER-MEMBRANE PROTEIN OF NEISSERIA-GONORRHOEAE [J].
BEUCHER, M ;
SPARLING, PF .
JOURNAL OF BACTERIOLOGY, 1995, 177 (08) :2041-2049
[4]   EFFECT OF OUTER-MEMBRANE VESICLE VACCINE AGAINST GROUP-B MENINGOCOCCAL DISEASE IN NORWAY [J].
BJUNE, G ;
HOIBY, EA ;
GRONNESBY, JK ;
ARNESEN, O ;
HOLSTFREDRIKSEN, J ;
HALSTENSEN, A ;
HOLTEN, E ;
LINDBAK, AK ;
NOKLEBY, H ;
ROSENQVIST, E ;
SOLBERG, LK ;
CLOSS, O ;
ENG, J ;
FROHOLM, LO ;
LYSTAD, A ;
BAKKETEIG, LS ;
HAREIDE, B .
LANCET, 1991, 338 (8775) :1093-1096
[5]   HUMAN IMMUNE-RESPONSE TO IRON-REPRESSIBLE OUTER-MEMBRANE PROTEINS OF NEISSERIA-MENINGITIDIS [J].
BLACK, JR ;
DYER, DW ;
THOMPSON, MK ;
SPARLING, PF .
INFECTION AND IMMUNITY, 1986, 54 (03) :710-713
[6]   EFFICACY, SAFETY, AND IMMUNOGENICITY OF A MENINGOCOCCAL GROUP-B (15-P1.3) OUTER-MEMBRANE PROTEIN VACCINE IN IQUIQUE, CHILE [J].
BOSLEGO, J ;
GARCIA, J ;
CRUZ, C ;
ZOLLINGER, W ;
BRANDT, B ;
RUIZ, S ;
MARTINEZ, M ;
ARTHUR, J ;
UNDERWOOD, P ;
SILVA, W ;
MORAN, E ;
HANKINS, W ;
GILLY, J ;
MAYS, J .
VACCINE, 1995, 13 (09) :821-829
[7]  
Bremner C, 1999, NEW ZEAL MED J, V112, P257
[8]   BACTERIAL ANTIGENIC VARIATION, HOST IMMUNE-RESPONSE, AND PATHOGEN-HOST COEVOLUTION [J].
BRUNHAM, RC ;
PLUMMER, FA ;
STEPHENS, RS .
INFECTION AND IMMUNITY, 1993, 61 (06) :2273-2276
[9]  
Buchanan SK, 1999, NAT STRUCT BIOL, V6, P56
[10]   Phase variation of the gonococcal siderophore receptor FetA [J].
Carson, SDB ;
Stone, B ;
Beucher, M ;
Fu, J ;
Sparling, PF .
MOLECULAR MICROBIOLOGY, 2000, 36 (03) :585-593