The objectives of this proposal were defined in order to obtain new knowledge on the molecular epidemiology of pneumococcal diseases and antibiotic resistance in different parts of the world, apply state-of-the-art technology to study host-pathogen interactions and apply innovative technologies for improving existing intervention strategies. Moreover, it would contribute towards the implementation of measures for prevention, control and treatment of pneumococcal diseases, especially those caused by multi-drug resistant strains. To achieve the purpose of this proposal, we have assembled a team with expertise required to fulfil the following objectives:

Objective 1:

Epidemiology of drug resistance and vaccine pressure replacement of S. pneumoniae

The major tasks of this objective will be to undertake monitoring of prevalent S. pneumoniae serotypes and their resistance profiles in various countries. This will also include the epidemiology of the serotype replacement in areas where pneumococcal vaccine is in use. Since the prevalence of serotypes as well as the magnitude and quality of drug resistance is different in different parts of the world, this objective will address the epidemiology of S. pneumoniae in six countries, which include an Asian and a South American country. These studies will determine the frequency of emergence of antibiotical resistance, particularly in those serotypes that have potential to spread rapidly in the community. The second part of this objective will be to determine the changes in pneumococcal disease after introduction of the 7-valent pneumococcal conjugate vaccine in different regions.

Objective 2: 

Analysis of host-pathogen interactions and identification of potential therapeutic targets and vaccine candidates

A prerequisite for developing new control strategies is the detailed understanding of the interaction between pneumococcus and the host cells. The analysis of host-pathogen interaction will include the prevalent virulent strains, which will be continuously identified in the work packages dealing with the epidemiological studies. The molecular mechanisms of host-pathogen interactions will be elucidated by applying genomics and cell biological approaches. Identification and characterization of the factors involved will be an important part of objective 2. The biological functions of these factors will be determined by using pathogenicity tests involving cell cultures as well as animal models of pneumococcal diseases.

Objective 3: 

Development of improved vaccine and intervention strategies

This objective deals with the development of new therapeutic and vaccine tools against pneumococcal infections based on the knowledge generated in objectives 1 and 2. For designing new therapeutics, the molecular basis of pathogen recognition through specific components of pneumococcal cell wall by host proteins will be identified by using a structural biological approach. In the area of vaccine development, this objective will deal with a novel polysaccharide glycolipid conjugate vaccine as well as the development of a protein-based universal vaccine.