Dissecting the protection mechanism of new generation vaccines by synchronizing systems biology with in vivo imaging

ended

Despite successful reduction of the burden of many infectious diseases by vaccination and the strong improvement of vaccine safety, there is a strong need to improve existing vaccines and to develop new affordable vaccines with greater efficacy. Particle-based vaccines are one of the recent advances, with potentially a promising impact on global public health. Besides being investigated for their protective potential, the knowledge about their mechanism of protection is still scarce. VacTrack is designed to investigate this by innovatively combining state of the art in vivo imaging with global transcriptome analyses. I aim to dissect the route vaccines acquire inside the host along with the spatio-temporal changes in gene expression following vaccine exposure to the host, by utilizing pneumococcal antigens grafted to outer membrane vesicles (OMVs) as model formulations in imaging-assisted in vivo mouse vaccination and challenge infection models. VacTrack is expected to generate insights about novel pathways triggered in host following vaccination which will be further validated by an ex vivo approach via stimulation of murine and human whole blood. By exploiting systems biology, high resolution in vivo imaging and immunological approaches VacTrack will provide a blue print for the approach to study mechanism of protection of vaccines in general. Comprehension of correlates of protection by combining in vivo and ex vivo analyses will 1) help devise new pneumococcal vaccines, 2) improve existing vaccine formulations, 3) transform the direction of vaccine research by allowing targeting of specific novel pathways identified via VacTrack. Taken together, this proposal holds great potential in advancing the vaccine research to devise new and better vaccines to save and improve human lives on a global level.