Transcriptomics and Systems Biology analysis of human response to live attenuated viral vaccines

In the past century, vaccination was probably the most successful medical intervention to prevent death and morbidity due to infectious diseases. In this thesis work, a “systems vaccinology” approach was applied in two human clinical trials where healthy volunteers were vaccinated (i) with the Yellow Fever live attenuated vaccine (YF-17D, Stamaril, Sanofi-Pasteur) or (ii) with the live recombinant Ebola vaccine (rVSV-ZEBOV, Ervebo, Merck). After a brief introduction concerning the Systems biology approach for the study of vaccines, focusing on the use of transcriptomic analysis, this work also provides a summary about the topics discussed during the Sao Paulo School of Advanced Science on Vaccines (November 2018). The main topic of this work is the study of blood transcriptomic response in subjects vaccinated with a single dose of YF-17D: we demonstrated the presence of a vaccine-induced circadian regulation involving the immune response (further studies need to be led to investigate the role in circadian rhythm-related responses to vaccines). We also reported the results of transcriptomic analysis of the immune response to rVSV-ZEBOV (first vaccine licensed against Ebolavirus). The conclusion of this thesis work emphasizes how the transcriptomic approach is useful to characterize the type of immune response induced by vaccination. The use of computational approaches is essential to integrate information in order to identify molecular signatures associated to vaccine response and can also give new insights into vaccine immune response.