Molecular basis for the selection of vaccine candidates to be included in a new anti pertussis formulation

BOTTERO D.; GAILLARD M.; HOZBOR D.

Baltimore - EEUU

Simposio; Ninth International Bordetella Symposium.; 2010

Studies on Bordetella pertussis bacterial population divergence has not only allow advancing in the knowledge of this topic but also incorporating methodologies that can be applied in different fields of the knowledge. One possible application of these methodologies is in the selection of vaccine candidates to be included in a new formulation that is need to be effective even against the bacterial population circulating. In this work, using proteomics and genetic strategies we have characterized comparatively two vaccine strains (Bp137 and Bp10536) and one clinical isolate (Bp106) circulating in our country (Argentina) which is considered to be representative of the local bacterial collection. By pulsed-field gel electrophoresis (PFGE) we found that the similarity between the vaccine strains is 0.64 and between vaccine strains and the local isolate of 0.62.  In relation to ptxS1and prn genotypes, the clinical isolate contain the variants ptxS1A, prn2 while Bp137 ptxS1noA, prn1 and for Bp10536 ptxS1noA, without data on prn. By comparative proteomic studies of surface proteins, from a total 56 peptide subunits identified, 17 were differentially expressed between the three strains/isolates studied. An interesting aspect to emphasize is that the vaccine strain Bp137 expresses seven peptide subunits that are detected in the clinical isolate proteomic profile but are absent in the other vaccine strain. Moreover, this vaccine strain expresses a protein of TTSS which was previously reported as exclusively present in clinical isolates. Thirteen of the 17 peptide subunits are not expressed by Bp10536. To analyze whether these differences could have implications on pertussis vaccine protection we performed functional assay using the mice intranasal challenge model. By this assay we observed that the strain Bp137 gives better protection against local isolate than against the reference strain Bp18323. In contrast Bp10536 strain protects better against the reference strain than the local isolate. All these data show the strain Bp137 as an interesting candidate to be included in a vaccine that would be more effective against strains circulating in Argentina than Bp10536.