Recombinant polypeptides for antigenic mimicry of bacterial surface polysaccharides

Project: PHD

Project Details

Description

To address efficiently the development polypeptide antigens (surrogate antigens) which mimic bacterial polysaccharides (nominal antigens) the projects links research groups qualified in all known techniques for producing peptide- and antibody-based surrogate antigens.
The distinct approaches consist in the production of i) murine and ii) human single chain fragment anti-idiotype antibodies, and stabilised peptide libraries expressed on the surface of iii) bacteriophages and iv) bacteria and v) produced in vitro. The different strategies are chosen because they each have a different balance of technically ease and applicability to industrial exploitation. Even though methods i and ii may not directly lead to a human vaccine the sequence of the active peptide permits the screening of secondary peptide libraries.
The project will be undertaken in response to the need for effective vaccines for bacteria where a protective human immune-response is often restricted to the polysaccharide surface (capsular) antigens. In Brucella vaccination with whole LPS makes serological distinction of infection and vaccination impossible, while in Vibrio, the capsular polysaccharide exhibit poor immunogenicity and high crossreactivity have been reported for sugar based. In S. pneumoniae conjugate vaccines will not provide a complete solution for the problems with the current vaccine. Since expression of peptides on the surface of bacteria enhances antigen presentation by dendritic cells selected mimotopes will be displayed on recombinant bacteria.
The single parameters evaluated in this comparative approach are: 1) efficiency for producing the requested reagents; 2) specificity of the produced reagents; 3) antigenicity of the mimotopes; 4) protective efficacy in vaccine models. As not bias the results through analysis in a single vaccine model reagents will be developed to three different sugars of three different pathogens.
StatusFinished
Effective start/end date1/09/0131/12/03

Keywords

  • ScFv
  • Brucella
  • mimotope
  • phage display
  • Peptidomimetic