TY - JOUR
T1 - Spermidine enhances the efficacy of adjuvant in HBV vaccination in mice
AU - Ito, Daisuke
AU - Ito, Hiroyasu
AU - Ando, Tatsuya
AU - Sakai, Yasuhiro
AU - Ideta, Takayasu
AU - Ishii, Ken J.
AU - Ishikawa, Tetsuya
AU - Shimizu, Masahito
N1 - Publisher Copyright:
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.
PY - 2023/4
Y1 - 2023/4
N2 - Background: Various vaccine adjuvants have been developed to eliminate HBV from patients with chronic HBV infection. In addition, spermidine (SPD), a type of polyamine, has been reported to enhance the activity of immune cells. In the present study, we investigated whether the combination of SPD and vaccine adjuvant enhances the HBV antigen-specific immune response to HBV vaccination. Methods: Wild-type and HBV-transgenic (HBV-Tg) mice were vaccinated 2 or 3 times. SPD was orally administered in drinking water. Cyclic guanosine monophosphate-AMP (cGAMP) and nanoparticulate CpG-ODN (K3-SPG) were used as the HBV vaccine adjuvants. The HBV antigen-specific immune response was evaluated by measuring the HBsAb titer in blood collected over time and the number of interferon-γ producing cells by enzyme-linked immunospot assay. Results: The administration of HBsAg + cGAMP + SPD or HBsAg + K3-SPG + SPD significantly enhanced HBsAg-specific interferon-γ production by CD8 T cells from wild-type and HBV-Tg mice. The administration of HBsAg, cGAMP, and SPD increased serum HBsAb levels in wild-type and HBV-Tg mice. In HBV-Tg mice, the administration of SPD + cGAMP or SPD + K3-SPG with HBV vaccination significantly reduced HBsAg levels in the liver and serum. Conclusions: These results indicate that the combination of HBV vaccine adjuvant and SPD induces a stronger humoral and cellular immune response through T-cell activation. These treatments may support the development of a strategy to completely eliminate HBV.
AB - Background: Various vaccine adjuvants have been developed to eliminate HBV from patients with chronic HBV infection. In addition, spermidine (SPD), a type of polyamine, has been reported to enhance the activity of immune cells. In the present study, we investigated whether the combination of SPD and vaccine adjuvant enhances the HBV antigen-specific immune response to HBV vaccination. Methods: Wild-type and HBV-transgenic (HBV-Tg) mice were vaccinated 2 or 3 times. SPD was orally administered in drinking water. Cyclic guanosine monophosphate-AMP (cGAMP) and nanoparticulate CpG-ODN (K3-SPG) were used as the HBV vaccine adjuvants. The HBV antigen-specific immune response was evaluated by measuring the HBsAb titer in blood collected over time and the number of interferon-γ producing cells by enzyme-linked immunospot assay. Results: The administration of HBsAg + cGAMP + SPD or HBsAg + K3-SPG + SPD significantly enhanced HBsAg-specific interferon-γ production by CD8 T cells from wild-type and HBV-Tg mice. The administration of HBsAg, cGAMP, and SPD increased serum HBsAb levels in wild-type and HBV-Tg mice. In HBV-Tg mice, the administration of SPD + cGAMP or SPD + K3-SPG with HBV vaccination significantly reduced HBsAg levels in the liver and serum. Conclusions: These results indicate that the combination of HBV vaccine adjuvant and SPD induces a stronger humoral and cellular immune response through T-cell activation. These treatments may support the development of a strategy to completely eliminate HBV.
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U2 - 10.1097/HC9.0000000000000104
DO - 10.1097/HC9.0000000000000104
M3 - Article
C2 - 36972390
AN - SCOPUS:85164905777
SN - 2471-254X
VL - 7
JO - Hepatology Communications
JF - Hepatology Communications
IS - 4
M1 - e0104
ER -
