Induction of humoral and cellular immune response to HBV vaccine can be up-regulated by STING ligand

Hiroyasu Ito; Ayumu Kanbe; Akira Hara; Tetsuya Ishikawa

doi:10.1016/j.virol.2019.03.013

Induction of humoral and cellular immune response to HBV vaccine can be up-regulated by STING ligand

Hiroyasu Ito, Ayumu Kanbe, Akira Hara, Tetsuya Ishikawa

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

15 Citations (Scopus)

Abstract

A persistent hepatitis B virus (HBV) infection is characterized by a lack of or a weak immune response to HBV. Efficient induction of the HBV-specific immune response leads to the clearance of HBV. Stimulator of interferon (IFN) genes (STING) is a cytoplasmic sensor of intracellular DNA from microbes and host cells. In the present study, we examined the efficacy of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) that is a ligand of the STING pathway as an HBV vaccine adjuvant. Wild-type (WT) mice and HBV-transgenic (HBV-Tg) mice were immunized with hepatitis B surface antigen (HBsAg) and cGAMP. The vaccination with HBsAg and cGAMP significantly enhanced the humoral and cellular immune response to HBsAg in WT and HBV-Tg mice. Cytokine production related to Th1 and Th2 responses and the activation of antigen-presenting cells in lymphoid tissues were induced by cGAMP. Vaccination using cGAMP may overcome tolerance in patients with chronic HBV infection.

Original language	English
Pages (from-to)	233-239
Number of pages	7
Journal	Virology
Volume	531
DOIs	https://doi.org/10.1016/j.virol.2019.03.013
Publication status	Published - 05-2019
Externally published	Yes

All Science Journal Classification (ASJC) codes

Virology

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10.1016/j.virol.2019.03.013

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title = "Induction of humoral and cellular immune response to HBV vaccine can be up-regulated by STING ligand",

abstract = "A persistent hepatitis B virus (HBV) infection is characterized by a lack of or a weak immune response to HBV. Efficient induction of the HBV-specific immune response leads to the clearance of HBV. Stimulator of interferon (IFN) genes (STING) is a cytoplasmic sensor of intracellular DNA from microbes and host cells. In the present study, we examined the efficacy of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) that is a ligand of the STING pathway as an HBV vaccine adjuvant. Wild-type (WT) mice and HBV-transgenic (HBV-Tg) mice were immunized with hepatitis B surface antigen (HBsAg) and cGAMP. The vaccination with HBsAg and cGAMP significantly enhanced the humoral and cellular immune response to HBsAg in WT and HBV-Tg mice. Cytokine production related to Th1 and Th2 responses and the activation of antigen-presenting cells in lymphoid tissues were induced by cGAMP. Vaccination using cGAMP may overcome tolerance in patients with chronic HBV infection.",

author = "Hiroyasu Ito and Ayumu Kanbe and Akira Hara and Tetsuya Ishikawa",

note = "Funding Information: We are grateful to Francis V. Chisari for providing HBsAg transgenic mice lineage 107-5D. This research is partially supported by the grant from Japan Agency for Medical Research and development, AMED . Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = may,

doi = "10.1016/j.virol.2019.03.013",

language = "English",

volume = "531",

pages = "233--239",

journal = "Virology",

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AU - Ito, Hiroyasu

AU - Kanbe, Ayumu

AU - Hara, Akira

AU - Ishikawa, Tetsuya

N1 - Funding Information: We are grateful to Francis V. Chisari for providing HBsAg transgenic mice lineage 107-5D. This research is partially supported by the grant from Japan Agency for Medical Research and development, AMED . Publisher Copyright: © 2019

PY - 2019/5

Y1 - 2019/5

N2 - A persistent hepatitis B virus (HBV) infection is characterized by a lack of or a weak immune response to HBV. Efficient induction of the HBV-specific immune response leads to the clearance of HBV. Stimulator of interferon (IFN) genes (STING) is a cytoplasmic sensor of intracellular DNA from microbes and host cells. In the present study, we examined the efficacy of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) that is a ligand of the STING pathway as an HBV vaccine adjuvant. Wild-type (WT) mice and HBV-transgenic (HBV-Tg) mice were immunized with hepatitis B surface antigen (HBsAg) and cGAMP. The vaccination with HBsAg and cGAMP significantly enhanced the humoral and cellular immune response to HBsAg in WT and HBV-Tg mice. Cytokine production related to Th1 and Th2 responses and the activation of antigen-presenting cells in lymphoid tissues were induced by cGAMP. Vaccination using cGAMP may overcome tolerance in patients with chronic HBV infection.

AB - A persistent hepatitis B virus (HBV) infection is characterized by a lack of or a weak immune response to HBV. Efficient induction of the HBV-specific immune response leads to the clearance of HBV. Stimulator of interferon (IFN) genes (STING) is a cytoplasmic sensor of intracellular DNA from microbes and host cells. In the present study, we examined the efficacy of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) that is a ligand of the STING pathway as an HBV vaccine adjuvant. Wild-type (WT) mice and HBV-transgenic (HBV-Tg) mice were immunized with hepatitis B surface antigen (HBsAg) and cGAMP. The vaccination with HBsAg and cGAMP significantly enhanced the humoral and cellular immune response to HBsAg in WT and HBV-Tg mice. Cytokine production related to Th1 and Th2 responses and the activation of antigen-presenting cells in lymphoid tissues were induced by cGAMP. Vaccination using cGAMP may overcome tolerance in patients with chronic HBV infection.

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JO - Virology

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Induction of humoral and cellular immune response to HBV vaccine can be up-regulated by STING ligand

Abstract

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