A therapeutic hepatitis B mRNA vaccine with strong immunogenicity and persistent virological suppression

Huajun Zhao; Xianyu Shao; Yating Yu; Lulu Huang; Narh Philip Amor; Kun Guo; Changzhen Weng; Weijun Zhao; Ailu Yang; Jiesen Hu; Hongbao Yang; Zhenguang Liu; Qiuju Han; Leilei Shi; Shiyu Sun; Jian Zhang; Ang Lin; Yong Yang

doi:10.1038/s41541-024-00813-3

A therapeutic hepatitis B mRNA vaccine with strong immunogenicity and persistent virological suppression

NPJ Vaccines. 2024 Feb 3;9(1):22. doi: 10.1038/s41541-024-00813-3.

Authors

Huajun Zhao^#¹, Xianyu Shao^#^{2

3}, Yating Yu^#⁴, Lulu Huang^#^{2

3}, Narh Philip Amor^#^{2

3}, Kun Guo^{2

3}, Changzhen Weng^{2

3}, Weijun Zhao^{2

3}, Ailu Yang⁴, Jiesen Hu⁵, Hongbao Yang³, Zhenguang Liu⁶, Qiuju Han⁴, Leilei Shi⁷, Shiyu Sun⁸, Jian Zhang⁹, Ang Lin^{10

11}, Yong Yang^{12

13

14}

Affiliations

¹ Institute of Immunopharmaceutical Sciences, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China. zhaohuajun89@sdu.edu.cn.
² Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
³ Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, China.
⁴ Institute of Immunopharmaceutical Sciences, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
⁵ Firestone Biotechnologies, Shanghai, China.
⁶ College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
⁷ Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁸ Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
⁹ Institute of Immunopharmaceutical Sciences, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China. zhangj65@sdu.edu.cn.
¹⁰ Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China. anglin@cpu.edu.cn.
¹¹ Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, China. anglin@cpu.edu.cn.
¹² Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China. yy@cpu.edu.cn.
¹³ Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, China. yy@cpu.edu.cn.
¹⁴ School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, PR China. yy@cpu.edu.cn.

^# Contributed equally.

Abstract

Here we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.3), this vaccine demonstrates sufficient and persistent virological suppression, and robust immunogenicity in terms of induction of strong innate immune activation, high-level virus-specific antibodies, memory B cells and T cells. mRNA platform therefore holds prospects for therapeutic vaccine development to combat CHB.

Abstract

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