Study on the Effect of Chimeric Virus-like Particles Based on Hepatitis E Virus on Human Papillomavirus Type 16 Tumor Immunotherapy
10.13748/j.cnki.issn1007-7693.20230543
- VernacularTitle:基于戊肝病毒的嵌合病毒样颗粒对人乳头瘤病毒16型肿瘤免疫治疗作用的研究
- Author:
Kexin ZHANG
1
;
Yun ZHU
1
;
Peikai MA
1
;
Tong AN
1
;
Siqi LI
1
;
Qiantong SHEN
1
;
Gang CHEN
1
,
2
,
3
;
Yongneng LUO
4
;
Fangchng ZHUANG
1
,
2
,
3
;
Shaohong LU
1
,
2
,
3
;
Meng GAO
1
,
2
,
3
Author Information
1. Hangzhou Medical College, School of Basic Medicine Sciences and Forensic Medicine, Hangzhou 310007, China
2. Hangzhou Medical College, Medical and Biological Vaccine R and D Key Lab of Zhejiang Province, Hangzhou 310007, China
3. Hangzhou Medical College, Zhejiang Engineering Research Center of New Vaccine, Hangzhou 310007, China
4. Hangzhou Medical College, Shool of Laboratory Medicine, Hangzhou 310007, China
- Publication Type:Journal Article
- Keywords:
human papillomavirus type 16;
prokaryotic expression;
immunogenicity
- From:
Chinese Journal of Modern Applied Pharmacy
2023;40(23):3251-3256
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the immunotherapeutic effect of chimeric virus-like particles(VLPs) based on hepatitis E virus(HEV) against human papillomavirus type 16(HPV 16) tumor. METHODS HPV16 E7 was inserted into the p239 protein of HEV to form the recombinant chimeric protein p239-HPV16 E7. The constructed recombinant protein was expressed by Escherichia coli, purified, and then refolded, and the protein was detected by electron microscopy and dynamic light scattering to confirm size and shape. Then, the C57B/L mice were immunized with the protein grain, and the lymphocyte differentiation of mouse spleen was detected by flow cytometry and enzyme-linked immune spot immunoassay; in addition, TC-1 tumor cells were used to construct tumor models in C57B/L mice to evaluate the anti-tumor immune effect of protein particles in mice. RESULTS After refold in vitro, the structure of chimeric protein was observed under electron microscopy, and the size of particle was 22.80 nm. The obtained protein particles induced favorable specific cellular immune response in C57B/L mice. Compared with the control group, the proportions of CD3+/CD4+ and CD3+/CD8+ in spleen lymphocytes of experimental groups were significantly different(P＜0.05), and effector T cells secreting IFN-γ interferon were also increased remarkably. At the same time, the obtained protein particles could effectively inhibit the growth of tumor cells in TC-1 tumor-bearing mice, and the mice did not die during the experimental period, while the tumors in the control mice grew rapidly and all died after 6 weeks. CONCLUSION Chimeric protein p239-HPV16E7 which was expressed in prokaryotes can form virus-like particles and effectively induce anti-tumor immunity against HPV16.
