Hantavax is an inactivated vaccine for hemorrhagic fever with renal syndrome (HFRS). The immunogenic responses have not been elucidated yet. Here we conducted a cohort study in which 20 healthy subjects were administered four doses of Hantavax during 13-months period. Pre- and post- vaccinated peripheral blood mononuclear cells (PBMCs) and sera were analysed by transcriptomic and metabolomic profilings, respectively. 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, octanoyl-carnitine, tyrosine, ubiquinone-9, and benzoate were significantly elevated in HRs, while chenodeoxycholic acid and methyl palmitate were upregulated in NRs and LRs, compared with 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. Collectively, our data provide new insight into the underlying mechanisms of the Hantavax-mediated immunogenicity in humans.
Bibliographical noteFunding Information:
We thank the participants, and study coordinators (Mi Suk Lee, Eun Mi Yu, Eun Jeong Kim) for their help in recruitment, vaccination and follow up of participants. This study was supported by grants from Green Cross Corporation, Yongin, Republic of Korea. The sponsor participated in the clinical trial design, execution, and the data collections. Although the sponsor reviewed the penultimate draft, the opinions expressed are those of the authorship and may not necessarily reflect those of the sponsor. This research was also supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF-2017R1A2B4003890).
© 2019, The Author(s).
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