Study of a virus-like particle vaccine containing N-terminal epitopes of human papilloma virus L2 protein
10.3969/j.issn.1000-484X.2016.03.016
- VernacularTitle:人乳头瘤病毒L2蛋白的病毒样颗粒疫苗研究
- Author:
Rong JIANG
;
Junqiang LI
;
Mingming YANG
;
Tao ZHU
;
Xuefeng YU
;
Zhongqi SHAO
- Publication Type:Journal Article
- Keywords:
Human papillomavirus;
L2 peptide;
Hepatitis B virus core antigen;
Virus-like particles;
Immunogenicity;
Neutralization antibody
- From:
Chinese Journal of Immunology
2016;32(3):366-371
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare a virus-like particle (VLP),containing Hepatitis B virus core antigen (HBcAg) and N-terminal peptides of the L2 protein of human papilloma virus (HPV),and investigate the immunogenicity of the VLP in mice and the protection against different strains of HPV .Methods:A fusion gene was synthesized to insert a DNA fragment ,coding for the N-terminal epitopes of the L2 protein of HPV16,into the HBcAg coding sequence;HBc-L2 fusion protein was highly expressed in E.coli using the pET9a and BL21(DE3) expression system;the purified fusion protein was used to immunize BALB/c mice and antibody titers against the L2 epitopes in mouse sera were determined by indirect ELISA;the levels of neutralizing antibodies against both HPV 16 and 18 were also analyzed.Results:HBc-L2 fusion protein was expressed in E.coli and purified,with the purity >80%,by ammonium sulfate pre-cipitation and CL-4B gel filtration;analysis of the purified fusion protein ,using size exclusion chromatography with multi-angle laser light scattering detection ( SEC-MALS) and electron microscope ,revealed that HBc-L2 was assembled into a stable VLP structure auto-matically following its expression;immunization of BALB/c mice with the purified VLPs resulted in high antibody titers in mouse sera against the L2 epitopes;furthermore,it was demonstrated that the sera from the immunized mice had neutralization activities against both HPV16 and HPV18.Conclusion:The immunogenicity of the L2 epitopes was highly enhanced by the construction of HBc-L2 fusion protein and the formation of the VLP structure;the fusion protein was also capable of inducing protections against different serotypes of HPV,therefore,it could be a potential HPV vaccine with a broad coverage and low production cost .
