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

Autor: Yunlong Hu, Li Tang, Zhengyu Zhu, He Meng, Tingting Chen, Sheng Zhao, Zhenchao Jin, Zhulin Wang, Guangyi Jin
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-14 (2020)
Druh dokumentu: article
ISSN: 1479-5876
DOI: 10.1186/s12967-020-02275-2
Popis: Abstract Background 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. Methods 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. Results 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 evidenced by an increased HBsAg-specific IgG2a titer and a T-cell response in normal mice compared to mice received traditional Alum-adjuvant HBV vaccine. Importantly, T7-EA could break immune tolerance and induce persistent HBsAg-specific antibody and T-cell responses in an HBV mouse model. Conclusions T7-EA might be a candidate adjuvant in a prophylactic and therapeutic HBV vaccine.
Databáze: Directory of Open Access Journals
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