Immunizations with hepatitis B viral antigens and a TLR7/8 agonist adjuvant induce antigen-specific immune responses in HBV-transgenic mice

Ying Wang, Kun Chen, Zhiyuan Wu, Yuetao Liu, Shangmei Liu, Zhongmei Zou, Shu Hsia Chen, Chunfeng Qu

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background: The capacity of toll-like receptor (TLR) 7/8 agonist-conjugated hepatitis B virus (HBV) proteins (HBV-Ag) to overcome established hepatitis B surface antigen (HBsAg)-specific immune tolerance was explored. Methods: A TLR7/8 agonist, CL097, was conjugated with alum-absorbed HBsAg and hepatitis B core antigen (HBcAg), as confirmed by ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS). Mice from two independently generated HBV-transgenic (HBV-Tg) colonies, C57BL/6J-TgN (AlblHBV) 44Bri/J mice and C57BL/6-HBV-1.3 genome-eq mice, were immunized with CL097-conjugated HBV-Ag every 2 weeks, four times. Results: After immunization, 8/11 (72.7%) of the AlblHBV mice and 10/13 (76.9%) of the HBV-1.3 genome-eq mice generated serum detectable antibodies against HBsAg (anti-HBs). HBsAg-specific interferon gamma (IFN-γ)-producing CD4+ and CD8+ T-cells were detected in splenocytes from these mice. Naïve normal mice receiving splenocytes from the mice immunized with CL097-conjugated HBV-Ag generated immediate recall immune responses, e.g., the mice that received CD4+CD25+-depleted splenocytes generated anti-HBs on day 3 after HBsAg challenge while those receiving cells from sham-immunized mice did not. Conclusions: Immunization with CL097-conjugated HBV-Ag reversed immune tolerance in HBV-Tg mice and induced antigen-specific immune responses. TLR7/8 agonists appear to be potent adjuvants for the induction of antigen-specific Th1 responses in an immune tolerant state.

Original languageEnglish (US)
Pages (from-to)31-36
Number of pages6
JournalInternational Journal of Infectious Diseases
Volume29
DOIs
StatePublished - Dec 1 2014

Keywords

  • Antigen-specific Th1 responses
  • Chronic hepatitis B virus infection
  • Immune tolerant state
  • Toll-like receptor 7/8 agonists

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Immunizations with hepatitis B viral antigens and a TLR7/8 agonist adjuvant induce antigen-specific immune responses in HBV-transgenic mice'. Together they form a unique fingerprint.

Cite this