Pneumococcal vaccine escape: genome-wide characterisation of recombinants arising after vaccine implementation. (360G-Wellcome-079126_Z_06_Z)
Streptococcus pneumoniae (the 'pneumococcus') is one of the leading causes of childhood morbidity and mortality worldwide. A heptavalent conjugate vaccine (hereafter 'vaccine') is highly effective, but limited in its serotype coverage. There is evidence from large-scale national surveillance in the USA (the first country to implement the vaccine) that both pre-existing strains and vaccine-escape mutants of non-vaccine serotype 19A are emerging. These novel escape mutants, as determined by MLST, appear to originate from recombination between a vaccine serotype 4 and a non-vaccine serotype 19A. The expertise of the Centers for Disease Control (CDC) Atlanta, USA and Oxford University will be combined in this study. The CDC is conducting the largest ongoing surveillance of invasive pneumococcal disease post-vaccine implementation anywhere in the world; the Oxford investigators provide access to new high-throughput genome-wide sequence techniques, new methods for phylogenetic analysis and knowledge of pneumococcal molecular epidemiology. This investigation will use Affymetrix re-sequencing arrays and microarray analysis to compare pre- and post-vaccine genotypes with type 4 and 19A capsules to the 19A vaccine-escape recombinants. The data will be analysed to determine the genetic basis by which these recombinants have evolved and to predict possible future changes among pneumococci under vaccine selective pressure.
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Grant Details
Amount Awarded | 272904 |
Applicant Surname | Crook |
Approval Committee | Immunology and Infectious Disease Funding Committee |
Award Date | 2006-02-09T00:00:00+00:00 |
Financial Year | 2005/06 |
Grant Programme: Title | Project Grant |
Internal ID | 079126/Z/06/Z |
Lead Applicant | Prof Derrick Crook |
Other Applicant(s) | Prof Angela Brueggemann, Prof Peter Donnelly, Prof Timothy Peto |
Partnership Value | 272904 |
Planned Dates: End Date | 2010-03-31T00:00:00+00:00 |
Planned Dates: Start Date | 2006-10-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |