CpG Oligonucleotides Increase HBV-Specific Cytokine Responses in Whole Blood and Enhance Cytokine Release Assay Sensitivity

Dammermann et al., J Virol Methods (2017) - PMID: 28739303

Product(s) used in this publication: PepMix™ Peptide Pools



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. CpGoligonucleotides, as costimulators to increase diagnostic sensitivity and specificity of our HBV- specific cytokinereleaseassay.


Wholeblood 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 CpGoligonucleotides. IL2 and IFNγ secretion in plasma was assessed using ELISA.


CpGoligonucleotides specifically enhanced HBsAg-mediated IL2 (276±79pg/ml vs. 320±82pg/ml) and IFNγ (77±35pg/ml vs. 401±121pg/ml) responses in wholeblood. 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%.


We show that innate signals mediated via TLRs contribute to HBV-specific cellular immune responses. CpGoligonucleotides can be used to make wholeblood based cytokinerelease assays even more powerful as screening tools in HBV immunology.

Stay in touch and be the first to receive the latest news!