A Systems Vaccinology Approach Reveals the Mechanisms of Immunogenic Responses to Hantavax Vaccination in Humans

• Published in: Scientific reports 2019-03, Vol.9 (1), p.4760-4760, Article 4760
• Main Authors: Khan, Adnan, Shin, Ok Sarah, Na, Jinhyuk, Kim, Jae Kwan, Seong, Rak-Kyun, Park, Man-Seong, Noh, Ji Yun, Song, Joon Young, Cheong, Hee Jin, Park, Youngja Hwang, Kim, Woo Joo
• Format: Article
• Language: English
• Subjects: 101/58; 13/1; 38/47; 45/91; 631/250/590/1883; 631/337/2019; 692/308/53/2423; Adult; Aged; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antibody Formation - immunology; Antibody response; Arachidonic acid; Biosynthesis; Carnitine; CD69 antigen; Chenodeoxycholic acid; Clinical trials; Cytokines - blood; Drug dosages; Female; Fever; Folic acid; Gene expression; Hantaan virus - immunology; Hemorrhage; Hemorrhagic fever with renal syndrome; Hemorrhagic Fever with Renal Syndrome - immunology; Hemorrhagic Fever with Renal Syndrome - prevention & control; Hemorrhagic Fever with Renal Syndrome - virology; Humanities and Social Sciences; Humans; Immunity, Innate - immunology; Immunogenicity; Innate immunity; Leukocytes (mononuclear); Male; Medical schools; Medicine; Metabolites; Metabolome - physiology; Metabolomics; Middle Aged; multidisciplinary; Nicotinamide; Palmitic acid; Peripheral blood mononuclear cells; Principal components analysis; Science; Science (multidisciplinary); Thiamine; Transcriptome - genetics; Tumor necrosis factor-TNF; Tyrosine; Ubiquinone; University colleges; Vaccination; Vaccines; Vaccinology - methods; Viral infections; Viral Vaccines - immunology; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-41205-1

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.