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).

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Khan A, Shin OS, Na J, Kim JK, Seong RK, Park MS, Noh JY, Song JY, Cheong HJ, Park YH, Kim WJ