Project Outline

The primary purpose of the GPS project is to examine the effect of the rollout of pneumococcal conjugate vaccine on pneumococcal strains escaping the vaccine in developing countries through the sequencing and comparison of whole genome sequences of the species before and after vaccination.

It has the ambitious, but essential aim to reveal the repertoire of genes available to the pneumococcus to evade vaccination and is the largest human pathogen genome sequencing project attempted to date.

As antimicrobial resistant strains have emerged following conjugate vaccination in developed countries, a further goal of the GPS project is to discover the mechanisms by which the pneumococcus evades antimicrobials in the context of species survival following conjugate vaccination in developing countries.

The genome sequencing and bioinformatics expertise at the Sanger Institute will be focused in particular on the strategies of the pathogen to evade the human interventions of increasing antibiotic use and conjugate vaccine introduction in developing countries.

We will exploit the unique Global Strain Bank of pneumococcal strains from developing countries that were collected as part of a previous Gates funded PATH initiative at CDC/Emory University.

The project will include extensive collections of invasive pneumococcal strains collected before, during and after conjugate vaccine introduction in South Africa, The Gambia and Malawi. These include strains from HIV infected children and adults who are a key group in whom non-vaccine types may evolve.

We also have pre – vaccine strains from other developing countries that are beginning to introduce vaccine, and the proposal includes capacity to collect post vaccination strains from GAVI eligible countries post vaccination that are willing to share the DNA of their strains with us.

Overall the GPS project is funded to sequence the genomes sequencing of 20,000 strains of pneumococci

The strains to be sequenced will be accessed from a number of groups including those currently in the Global Strain Bank (3000) as well as isolates from South Africa (GERMS-SA)(4000), the Gambia and West Africa (3000) and Malawi (2000) as distributed above. In addition, we anticipate approaching additional partners from GAVI eligible developing countries for further isolate submission (up to 6000).

The pre PCV strains of IPD on the strain bank include all the Pneumococcal Molecular Epidemiology Network (PMEN) clones which are global in distribution and include all major antimicrobial resistant lineages.

In order to achieve a global perspective on the reservoir of genetic material available to the pneumococcus to evade PCV, we believe it essential to include strains from the country with the longest human intervention using PCV. Therefore we plan to sequence an additional 2000 strains from CDC’s Active Bacterial Core Surveillance (ABCs) program.

Funding for sequencing of 667 strains from children and adults, pre-PCV7, post-PCV7, and post-PCV13 will be found through co-funding for this proposal from internal mechanisms at the Sanger Institute and CDC.

This collaborative effort between Emory University’s Hubert Department of Global Health, Pathogen Genomics Group at the Wellcome Trust Sanger Institute, the National Institute for Communicable Diseases (NICD) within the South African National Health Laboratory Service, the MRC Research Unit in the Gambia, the University of Liverpool/Malawi-Liverpool-Wellcome Trust Clinical Research Programme (MLW) in Malawi and the CDC’s Respiratory Diseases Branch within the National Center for Immunization and Respiratory Diseases (NCIRD), represent a multidisciplinary group of lab scientists and researchers.

We have broad experience in the surveillance and research related to pathogens that cause vaccinepreventable diseases, in particular S.pneumoniae. This project will involve a consortium between major partners with the grant administered through Emory University with subcontracts to the NICD, MLW, MRC in Gambia, Sanger Institute and CDC Foundation.