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Heterogeneity of tbpB, the transferrin-binding protein B gene, among serogroup B Neisseria meningitidis strains of the ET-5 complex.

ABSTRACT: ET-5 complex strains of Neisseria meningitidis were traced intercontinentally and have been causing hyperendemic meningitis on a worldwide scale. In an attempt to develop a fully broad cross-reactive transferrin-binding protein B (TbpB)-based vaccine, we undertook to assess the extent of variability of TbpB proteins among strains of this epidemiological complex. For this purpose, a PCR-based method was developed to study the heterogeneity of the tbpB genes from 31 serogroup B N. meningitidis strains belonging to the ET-5 complex. To define adequate primers, the tbpB gene from an ET-5 complex strain, 8680 (B:15:P1.3; isolated in Chile in 1987), was cloned and the nucleotide sequence was determined and compared to two other previously published tbpB sequences. A tbpB fragment was amplified from genomic DNA from each of the 31 strains. By this method, heterogeneity in size was observed and further characterized by restriction pattern analysis with four restriction enzymes and by sequencing tbpB genes from three other ET-5 complex strains. Four distinct tbpB gene types were identified. Fifty-five percent of the strains studied (17/31) harbored tbpB genes similar to that of strain BZ83 (B:15:-) isolated in The Netherlands in 1984. Ten of the 31 strains (32.2%) had tbpB genes close to that of strain M982. Only 3 of the 31 (9.6%) were found to harbor tbpB genes close to that of strain 8680, and finally one strain, 8710 (B:15:P1.3; isolated in Chile in 1987), was found to harbor a tbpB gene different from all the others. These results demonstrated a pronounced variability among tbpB alleles within a limited number of ET-5 complex strains collected over a 19-year period. Despite the genetic heterogeneity observed, specific antisera raised to purified Tbps from ET-5 complex strains showed broad cross-reactivity between different TbpBs both by Western blot analysis and bactericidal assay, confirming that a limited number of TbpB molecules included in a vaccine are likely to induce broadly cross-reactive antibodies against the different strains.

SUBMITTER: Rokbi B

PROVIDER: S-EPMC170586 | biostudies-other | 1997 Sep

REPOSITORIES: biostudies-other

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Heterogeneity of tbpB, the transferrin-binding protein B gene, among serogroup B Neisseria meningitidis strains of the ET-5 complex.

Rokbi B B Mignon M M Caugant D A DA Quentin-Millet M J MJ

Clinical and diagnostic laboratory immunology 19970901 5

ET-5 complex strains of Neisseria meningitidis were traced intercontinentally and have been causing hyperendemic meningitis on a worldwide scale. In an attempt to develop a fully broad cross-reactive transferrin-binding protein B (TbpB)-based vaccine, we undertook to assess the extent of variability of TbpB proteins among strains of this epidemiological complex. For this purpose, a PCR-based method was developed to study the heterogeneity of the tbpB genes from 31 serogroup B N. meningitidis str ...[more]

PMID: 9302199

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Project description:The distribution of the two isotypes of tbpB in a collection of 108 serogroup B meningococcal strains belonging to the four major clonal groups associated with epidemic and hyperendemic disease (the ET-37 complex, the ET-5 complex, lineage III, and cluster A4) was determined. Isotype I strains (with a 1.8-kb tbpB gene) was less represented than isotype II strains (19.4 versus 80.6%). Isotype I was restricted to the ET-37 complex strains, while isotype II was found in all four clonal complexes. The extent of the allelic diversity of tbpB in these two groups was studied by PCR restriction analysis and sequencing of 10 new tbpB genes. Four major tbpB gene variants were characterized: B16B6 (representative of isotype I) and M982, BZ83, and 8680 (representative of isotype II). The relevance of these variants was assessed at the antigenic level by the determination of cross-bactericidal activity of purified immunoglobulin G preparations raised to the corresponding recombinant TbpB (rTbpB) protein against a panel of 27 strains (5 of isotype I and 22 of isotype II). The results indicated that rTbpB corresponding to each variant was able to induce cross-bactericidal antibodies. However, the number of strains killed with an anti-rTbpB serum was slightly lower than that obtained with an anti-TbpA(+)B complex. None of the sera tested raised against an isotype I strain was able to kill an isotype II strain and vice versa. None of the specific antisera tested (anti-rTbpB or anti-TbpA(+)B complex) was able to kill all of the 22 isotype II strains tested. Moreover, using sera raised against the C-terminus domain of TbpB M982 (amino acids 352 to 691) or BZ83 (amino acids 329 to 669) fused to the maltose-binding protein, cross-bactericidal activity was detected against 12 and 7 isotype II strains, respectively, of the 22 tested. These results suggest surface accessibility of the C-terminal end of TbpB. Altogether, these results show that although more than one rTbpB will be required in the composition of a TbpB-based vaccine to achieve a fully cross-bactericidal activity, rTbpB and its C terminus were able by themselves to induce cross-bactericidal antibodies.

Dataset Information

Heterogeneity of tbpB, the transferrin-binding protein B gene, among serogroup B Neisseria meningitidis strains of the ET-5 complex.

Publications

Heterogeneity of tbpB, the transferrin-binding protein B gene, among serogroup B Neisseria meningitidis strains of the ET-5 complex.

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