HantavaxTM vaccinated peripheral blood mononuclear cells (PBMCs) and sera analyses by transcriptomic and metabolomic profilings. HantavaxTM vaccinated peripheral blood mononuclear cells (PBMCs) and sera analyses by transcriptomic and metabolomic profilings

Purpose: To annotate vaccine-induced protective immunity following vaccination and identify the dynamics of enriched modules over time, and determine whether and how transcriptomics and metabolomics data correlates. charge ratio) within a range of ions set from 50 to 1,000 from mass spectral data. The data from triplicate run were averaged and statistically analysed using SIMCA 14.1 Results: Based on neutralizing antibody titers, subjects were subsequently classified into three groups; non responders (NRs), low responders (LRs) and high responders (HRs). Post vaccination differentially expressed genes (DEGs) associated with innate immunity and cytokine pathways were highly upregulated. DEG analysis revealed a significant induction of CD69 expression in the HRs. High resolution metabolomics (HRM) analysis showed that correlated to the antibody response, cholesteryl nitrolinoleate and octanoyl-carnitine were significantly elevated in HRs, while chenodeoxycholic acid and methyl palmitate were upregulated in NRs and LRs, but not HRs. Additionally, gene-metabolite interaction revealed upregulated gene-metabolite couplings in, folate biosynthesis, nicotinate and nicotinamide, arachidonic acid, thiamine and pyrimidine metabolism in a dose dependent manner in HR group. Conclusions: Our data provide new insight into the underlying mechanisms of the HantavaxTM-mediated immunogenicity in humans. Our study illustrate the potential for transcriptomics and untargeted metabolomics to identify genes and metabolites involved in immune responses which may propose a targeted vaccine design in future. Overall design: Systems vaccinology analyses were performed based on two different approaches: vaccination instance and responsiveness to the vaccine. In our study we vaccinated a total of 20 subjects with 4 doses. However, 1 subject (subject or sample # 3) was excluded from transcriptomic study after first vaccination due to abnormal antibody titer. Hence, we have 19 subjects vaccinated 4 time but the samples were collected before 1st and after 2nd, 3rd and 4th vaccination (i.e., sample collections was performed at 4 time points). This Series contains a total of 76 samples (19 x 4).