A novel TLR7 agonist as adjuvant to stimulate high quality HBsAg-specific immune responses in an HBV mouse model

Journal of Translational Medicine
Yunlong HuGuangyi Jin

Abstract

The global burden of hepatitis B virus (HBV) infection in terms of morbidity and mortality is immense. Novel treatments that can induce a protective immune response are urgently needed to effectively control the HBV epidemic and eventually eradicate chronic HBV infection. We designed and evaluated an HBV therapeutic vaccine consisting of a novel Toll-like receptor 7 (TLR7) agonist T7-EA, an Alum adjuvant and a recombinant HBsAg protein. We used RNA-seq, ELISA and hTLR7/8 reporting assays to characterize T7-EA in vitro and real-time PCR to evaluate the tissue-retention characteristics in vivo. To evaluate the adjuvant potential, we administrated T7-EA intraperitoneally in a formulation with an Alum adjuvant and HBsAg in normal and HBV mice, then, we evaluated the HBsAg-specific immune responses by ELISA and Elispot assays. T7-EA acted as an hTLR7-specific agonist and induced a similar gene expression pattern as an unmodified TLR7 ligand when Raw 264.7 cells were exposed to T7-EA; however, T7-EA was more potent than the unmodified TLR7 ligand. In vivo studies showed that T7-EA had tissue-retaining activity with stimulating local cytokine and chemokine expression for up to 7 days. T7-EA could induce Th1-type immune responses, as e...Continue Reading

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Citations

Jun 26, 2021·Frontiers in Immunology·Cong SunMu-Sheng Zeng
Jun 18, 2021·World Journal of Gastroenterology : WJG·Efthymios P TsounisChristos Triantos
Jul 27, 2021·Frontiers in Immunology·Jing SunYunzhang Hu
Oct 26, 2021·Frontiers in Cellular and Infection Microbiology·Yuanfa FengJun Huang

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Methods Mentioned

BETA
ELISA
PCR
flow cytometry
RNA-seq

Software Mentioned

Elispot
GraphPad Prism

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