1. Shmuel Willensky 10.4.2016 Computational tools seminar 1

2. Vaccines timeline http://shvarz.livejournal.com/416558.html 2

3. Polio Eradication 3

4. System Vaccinology 4

5. System Biology Essential Elements ∞Monitoring all components of the system in response to perturbation (vaccination in this case) ∞Integration of data from multiple types ∞Creation of mathematical models to predict the structure and behavior of the informational system ∞Validation of the models 5

6. Nature Immunology 10, 116 - 125 (2008) 6

7. ∞YF-17D has been administered to more than 600 million people worldwide ∞It confers protection to more than 90% of vaccinees ∞Despite its success, little is known about the mechanisms by which YF-17D induces effective immune responses In CD8 + T cells 7

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9. TIV vaccine (PBMCs) peripheral blood mononuclear cells (ASCs) antibody-secreting cells (GCs) germinal centers (TIV) trivalent inactivated influenza vaccine (LAIV) live attenuated influenza vaccine (mDC) myeloid DC (pDC) plasmacytoid DC (NK) natural killer 9

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11. (MCV4) meningococcus polysaccharide-protein conjugated vaccine (MPSV4) meningococcus polysaccharide-containing vaccines (YF-17D) yellow fever vaccine (TIV) trivalent inactivated influenza vaccine (LAIV) live attenuated influenza vaccine 11

12. Each segment on the circle corresponds to one vaccine dataset. In each segment, the inner circular bands show an ordered list of all BTM modules, layered by histograms of significantly correlated modules, red for positive correlation and blue for negative correlation. Each link inside the circles connects a significant that is common between different data sets. Modules common to three vaccines are linked in black, and their labels are marked by a black dot. Plasma and immunoglobulin modules are linked in green. blood transcriptional module (BTM) = highly connected genes with specific biological contexts 12

13. What’s next? ∞Further using the system vaccinology approach to clarify the mechanism of proved vaccines ∞Establish the “universal correlate” that predicts effective immune response in order to accelerate vaccine development processes 13

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