Young scientists win iGEM contest
Ljubljana – The most talented young synthetic biologists currently seem to be coming from Eastern Europe. After its success in 2006, a team of young undergraduate chemists from the University of Ljubljana has once again won the annual international Genetically Engineered Machine competition (iGEM), a contest to build synthetic biological systems from standard, interchangeable biological parts stored in the Registry of Standard Biological Parts. The group under Roman Jerala beat out 83 international research teams with two new strategies for designing and engineering vaccines from the “immunobricks”. Initial tests suggest that the synthetic vaccines they created can trigger a response of both the adaptive and the innate immune system. Mice that were injected with the synthetic vaccines produced antibodies against Helicobacter pylori. The bacteria that can cause gastritis, stomach ulcers and is linked to stomach cancer has developed strategies to bypass recognition by the immune system.
In a first approach, the student team re-engineered the H. pylori flagellin protein, which is able to avoid recognition by dendritic cells in the innate immune system because it does not activate host Toll-like receptor 5 (TLR5). To break this “flagellin stealth” in the ulcer bacterium, the Slovenian team fused parts of E.coli flagellin (FliC) to the N’- and the C-terminus of H. pylori flagellin (FlaA), subsequently adding a synthetic multiepitope containing parts of the strong H. pylori antigens Urease B, Adhesin A, and Vacuolyating Cytotoxin A to the C-terminus to elicit an antibody response. All three implementations of this system in the form of recombinant proteins, engineered bacteria and DNA vaccines triggered a strong immune response in mice.
The team then extended the range of activation of the innate immune response to different TLRs by designing a DNA vaccine that leads to expression of a fusion protein of the antigenic H. plylori multiepitope with different TLR segments, which are activated by dimerisation in the membrane (TLR4) of host cells or in endosomes (TLR3). Using this approach, the Slovenian students triggered an immune response against both pathogen antigens presented on the cell surface and on MHC II molecules presenting antigen fragments after processing in endosomes. The young researchers are now planning to carry out animal tests with the latter approach. B