A novel rapid modularized hepatitis B core virus-like particle-based platform for personalized cancer vaccine preparation via fixed-point coupling

Mei Ji; Jie Zhu; Xi-Xiu Xie; Dong-Qun Liu; Bin Wang; Zhuo Yu; Rui-Tian Liu

doi:10.1016/j.nano.2020.102223

A novel rapid modularized hepatitis B core virus-like particle-based platform for personalized cancer vaccine preparation via fixed-point coupling

Nanomedicine. 2020 Aug:28:102223. doi: 10.1016/j.nano.2020.102223. Epub 2020 May 16.

Authors

Mei Ji¹, Jie Zhu², Xi-Xiu Xie³, Dong-Qun Liu¹, Bin Wang³, Zhuo Yu⁴, Rui-Tian Liu⁵

Affiliations

¹ National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, China.
² National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, China.
⁴ Beijing Tsinghua Changgung Hospital, Changping District, Beijing, China. Electronic address: yza02214@btch.edu.cn.
⁵ National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, China. Electronic address: rtliu@ipe.ac.cn.

PMID: 32422220
DOI: 10.1016/j.nano.2020.102223

Abstract

Personalized cancer vaccine which targets neoepitopes shows great promise for cancer treatment. However, rapid preparation is a critical challenge for clinical application of personalized cancer vaccine. Genetic recombination and chemical modification are a time-consuming "trial and error" pattern for making vaccines. Here we first constructed a platform for peptide vaccine preparation by inserting SpyCatcher into the major immunodominant region (MIR) of hepatitis B core protein (HBc) (1-183). The resulted recombinant protein HBc_(1-183)-SpyCatcher (HBc_(1-183)-S) assembled to virus-like particles (VLPs) and readily bound to SpyTag conjugated with OVA epitope peptides by just mixing, forming HBc_(1-183)-S-OVA. HBc_(1-183)-S-OVA VLPs effectively induced dendritic cell maturation. Our further results indicated that HBc_(1-183)-S-OVA VLPs vaccination inhibited tumor growth in both prophylactic and treatment ways in E.G7-OVA tumor bearing mice by generating significant OVA-specific cytotoxic T lymphocyte responses. Our study provides a simple, rapid, efficient and universal HBc-based platform for the preparation of personalized cancer vaccine.

Keywords: Hepatitis B core protein; Personalized cancer vaccine; SpyCatcher/SpyTag; T cell epitope; Virus-like particle (VLP).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cancer Vaccines / immunology*
Cancer Vaccines / therapeutic use*
Cell Line
Dynamic Light Scattering
Female
Flow Cytometry
Hepatitis B Core Antigens / immunology*
Mice
Mice, Inbred C57BL
Microscopy, Electron, Transmission
Precision Medicine / methods
Vaccines, Virus-Like Particle / chemistry
Vaccines, Virus-Like Particle / immunology

Substances

Cancer Vaccines
Hepatitis B Core Antigens
Vaccines, Virus-Like Particle