A novel virus-like particle based on hepatitis B core antigen and substrate-binding domain of bacterial molecular chaperone DnaK.
Hepatitis B virus core (HBc) protein has been proved to be an attractive carrier for foreign epitopes, and can display green fluorescent protein (GFP) on its surface. The structure of substrate-binding domain of DnaK [DnaK (394-504 aa), DnaK SBD] is similar to GFP, we therefore reasoned that DnaK SBD might also be tolerated. Electron microscopic observations suggested that the chimeric proteins containing the truncated HBc (HBcDelta) and DnaK SBD could self-assemble into virus-like particle (VLP). Then the accessibility of DnaK SBD and the adjuvanticity of VLP HBcDelta-SBD were demonstrated by two recombinant peptide vaccines against gonadotropin-releasing hormone (GnRH), GhM and GhMNR. The latter carries in addition the peptide motif NRLLLTG which is known to bind to DnaK and DnaK SBD. The combination of VLP HBcDelta-SBD and GhMNR elicited stronger humoral responses and caused further testicular atrophy than the combinations of VLP HBcDelta and GhMNR or VLP HBcDelta-SBD and GhM in Balb/c mice. These findings indicate VLP HBcDelta-SBD might serve as an excellent carrier for GhMNR and some other peptide vaccines.
Wang
Xue Jun
XJ
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Hanzhong Road 140, Nanjing 210029, Jiangsu Province, People's Republic of China. wangxuejun1979728@hotmail.com
Gu
Kai
K
Xiong
Qi Yan
QY
Shen
Liang
L
Cao
Rong Yue
RY
Li
Ming Hui
MH
Li
Tai Ming
TM
Wu
Jie
J
Liu
Jing Jing
JJ
D000818:Animals; D001665:Binding Sites; D029968:Escherichia coli Proteins / Q000276:immunology*; D005822:Genetic Vectors; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013737:Testis / Q000166:cytology; D014614:Vaccines, Synthetic / Q000276:immunology
D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D007987:Gonadotropin-Releasing Hormone; C063842:dnaK protein, E coli