CpG oligonucleotides increase HBV-specific cytokine responses in whole blood and enhance cytokine release assay sensitivity
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CpG oligonucleotides increase HBV-specific cytokine responses in whole blood and enhance cytokine release assay sensitivity. / Dammermann, Werner; Dornbrack, Julia; Bröker, Katharina; Bentzien, Frank; Lüth, Stefan.
In: J VIROL METHODS, Vol. 248, 10.2017, p. 195-201.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CpG oligonucleotides increase HBV-specific cytokine responses in whole blood and enhance cytokine release assay sensitivity
AU - Dammermann, Werner
AU - Dornbrack, Julia
AU - Bröker, Katharina
AU - Bentzien, Frank
AU - Lüth, Stefan
N1 - Copyright © 2017 Elsevier B.V. All rights reserved.
PY - 2017/10
Y1 - 2017/10
N2 - BACKGROUND: Chronic hepatitis B leads to liver cirrhosis and hepatocellular carcinoma. To develop a therapeutic vaccine for chronic hepatitis B patients it is necessary to assess cellular immune responses to hepatitis B virus (HBV) antigens. We investigated the potential of toll-like receptor (TLR) 9 agonists, i.e. CpG oligonucleotides, as costimulators to increase diagnostic sensitivity and specificity of our HBV- specific cytokine release assay.METHODS: Whole blood from 80 healthy individuals (n=51 hepatitis B vaccinated, n=29 unvaccinated) was stimulated with hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (HBcAg) in presence or absence of CpG oligonucleotides. IL2 and IFNγ secretion in plasma was assessed using ELISA.RESULTS: CpG oligonucleotides specifically enhanced HBsAg-mediated IL2 (276±79pg/ml vs. 320±82pg/ml) and IFNγ (77±35pg/ml vs. 401±121pg/ml) responses in whole blood. When IFNγ release was considered as readout depicting the hepatitis B vaccination status, the according assay reached a diagnostic sensitivity of 61% without, but of 76% with additional CpG oligonucleotide stimulation at a diagnostic specificity of 90%.CONCLUSIONS: We show that innate signals mediated via TLRs contribute to HBV-specific cellular immune responses. CpG oligonucleotides can be used to make whole blood based cytokine release assays even more powerful as screening tools in HBV immunology.
AB - BACKGROUND: Chronic hepatitis B leads to liver cirrhosis and hepatocellular carcinoma. To develop a therapeutic vaccine for chronic hepatitis B patients it is necessary to assess cellular immune responses to hepatitis B virus (HBV) antigens. We investigated the potential of toll-like receptor (TLR) 9 agonists, i.e. CpG oligonucleotides, as costimulators to increase diagnostic sensitivity and specificity of our HBV- specific cytokine release assay.METHODS: Whole blood from 80 healthy individuals (n=51 hepatitis B vaccinated, n=29 unvaccinated) was stimulated with hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (HBcAg) in presence or absence of CpG oligonucleotides. IL2 and IFNγ secretion in plasma was assessed using ELISA.RESULTS: CpG oligonucleotides specifically enhanced HBsAg-mediated IL2 (276±79pg/ml vs. 320±82pg/ml) and IFNγ (77±35pg/ml vs. 401±121pg/ml) responses in whole blood. When IFNγ release was considered as readout depicting the hepatitis B vaccination status, the according assay reached a diagnostic sensitivity of 61% without, but of 76% with additional CpG oligonucleotide stimulation at a diagnostic specificity of 90%.CONCLUSIONS: We show that innate signals mediated via TLRs contribute to HBV-specific cellular immune responses. CpG oligonucleotides can be used to make whole blood based cytokine release assays even more powerful as screening tools in HBV immunology.
KW - Journal Article
U2 - 10.1016/j.jviromet.2017.07.011
DO - 10.1016/j.jviromet.2017.07.011
M3 - SCORING: Journal article
C2 - 28739303
VL - 248
SP - 195
EP - 201
JO - J VIROL METHODS
JF - J VIROL METHODS
SN - 0166-0934
ER -
