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

Adnan Khan; Ok Sarah Shin; Jinhyuk Na; Jae Kwan Kim; Rak Kyun Seong; Man Seong Park; Ji Yun Noh; Joon Young Song; Hee Jin Cheong; Youngja Hwang Park; Woo Joo Kim

doi:10.1038/s41598-019-41205-1

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

Adnan Khan, Ok Sarah Shin, Jinhyuk Na, Jae Kwan Kim, Rak Kyun Seong, Man Seong Park, Ji Yun Noh, Joon Young Song, Hee Jin Cheong, Youngja Hwang Park, Woo Joo Kim

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

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.

Original language	English
Article number	4760
Journal	Scientific reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-41205-1
Publication status	Published - 2019 Dec 1

Bibliographical note

Funding 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).

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-019-41205-1

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title = "A Systems Vaccinology Approach Reveals the Mechanisms of Immunogenic Responses to Hantavax Vaccination in Humans",

abstract = "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.",

author = "Adnan Khan and Shin, {Ok Sarah} and Jinhyuk Na and Kim, {Jae Kwan} and Seong, {Rak Kyun} and Park, {Man Seong} and Noh, {Ji Yun} and Song, {Joon Young} and Cheong, {Hee Jin} and Park, {Youngja Hwang} and Kim, {Woo Joo}",

note = "Funding 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). Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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AU - Seong, Rak Kyun

AU - Park, Man Seong

AU - Noh, Ji Yun

AU - Song, Joon Young

AU - Cheong, Hee Jin

AU - Park, Youngja Hwang

AU - Kim, Woo Joo

N1 - Funding 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). Publisher Copyright: © 2019, The Author(s).

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N2 - 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.

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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