BIOLOGY OF GENE-DELETED M. tuberculosis STRAINS- IMMUNOLOGICAL MARKER PROFILING
|Coordinator||Karolinska institutet - Institutionen för laboratoriemedicin, Novum|
|Funding from Vinnova||SEK 1 500 000|
|Project duration||September 2012 - March 2014|
Purpose and goal
The aim of the project was to develop a novel BCG vaccine using a rational design. Most of the TB vaccines use secreted antigens. We identified three novel candidates that are responsible for the M tuberculosis cell wall development. Several recombinant BCG strains were constructed that express the cell-wall associated antigens (Rv0447c), Rv2957 and Rv2958c. Pre-clinical models were performed and immune responses were successfully tested, the antigens have been filed for IP to prepare for future trials.
Results and expected effects
Immune responses were successfully detected against the new TB vaccine targets. We have been able to show strong cellular and antibody responses against recombinant Rv0447c, Rv2957 and Rv2958c vaccine targets; particularly the target Rv2958c turned out to be superior in inducing T-cells producing interferon and TNFalpha. The recombinant BCG, expressing the new target antigens is available for phase I clinical trials.
Approach and implementation
Immunogenicity has been tested in animal models and using immune cells from patients with TB or from healthy donors. Expression of the new TB vaccine candidates in BCG has been tested by molecular biology and by specific antibodies that have been developed in our laboratory. Analysis of immune responses has been achieved by tetramer analysis, by cytokine production and by detection of vaccine target specific antibodies. We found that the vaccine construct is safe and immunogenic.