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

Adnan Khan, Ok 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

Research output: Contribution to journalArticle

2 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 languageEnglish
Article number4760
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Fingerprint

Vaccination
Metabolomics
Genes
Hemorrhagic Fever with Renal Syndrome
Chenodeoxycholic Acid
Inactivated Vaccines
Niacinamide
Carnitine
Niacin
Thiamine
Benzoates
Neutralizing Antibodies
Folic Acid
Innate Immunity
Arachidonic Acid
Antibody Formation
Tyrosine
Blood Cells
Healthy Volunteers
Cohort Studies

ASJC Scopus subject areas

  • General

Cite this

A Systems Vaccinology Approach Reveals the Mechanisms of Immunogenic Responses to Hantavax Vaccination in Humans. / Khan, Adnan; Shin, Ok; 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.

In: Scientific Reports, Vol. 9, No. 1, 4760, 01.12.2019.

Research output: Contribution to journalArticle

@article{58b16cebf84a47fbacb2cfae73c172b4,
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 Ok Shin and Jinhyuk Na and Kim, {Jae Kwan} and Seong, {Rak Kyun} and Man-Seong Park and Noh, {Ji Yun} and Joon-Young Song and Hee-Jin Cheong and Park, {Youngja Hwang} and Kim, {Woo Joo}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-41205-1",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - A Systems Vaccinology Approach Reveals the Mechanisms of Immunogenic Responses to Hantavax Vaccination in Humans

AU - Khan, Adnan

AU - Shin, Ok

AU - Na, Jinhyuk

AU - Kim, Jae Kwan

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

PY - 2019/12/1

Y1 - 2019/12/1

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85063043679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063043679&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-41205-1

DO - 10.1038/s41598-019-41205-1

M3 - Article

C2 - 30886186

AN - SCOPUS:85063043679

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 4760

ER -