[A study on the inhibitory effect on transplanted tumor growth expressing HCV NS3 protein by HCV minigene vaccine based on invariant chain substitution in mice].
OBJECTIVE
To establish a transplanted tumor producing HCV NS3 protein in mice and study the therapeutic effect of minigene vaccine based on invariant chain substitution.


METHODS
SP2/0-NS3 cells expressing HCV NS3 antigen were injected subcutaneously into BALB/ c mice. After three days of inoculation, different therapeutical reagents were injected intramuscularly into different groups of mice. The boost immunization was carried out two weeks after the first immunization. The efficiency of HCV NS3 Th1 minigene vaccine was estimated after 60 days observation.


RESULTS
For saline, pCI-neo, pHCV-NS3 and pHCV-NS3-Th1 treated groups, the induction period needed for tumor growth was 16.17+/-2.55, 14.40+/-1.82, 16.75+/-2.36, and 24.00+/-5.57 days (t =2.623, P =0.034 vs saline, t =3.713, P =0.010 vs pCI-neo and t =2.425, P =0.045 vs pHCV-NS3) respectively. The tumorigenesis rates were 100%, 100%, 57.1% (8/14, chi2 = 6.190, P = 0.013 vs saline and chi2 = 6.608, P = 0.010 vs pCI-neo) and 46.7% (7/15, chi2 = 9.707, P = 0.002 vs saline and chi2 = 10.311, P = 0.001 vs pCI-neo ) respectively. The survival rates were 0, 0, 50.0% (7/14, chi2 = 5.787, P = 0.016 vs saline and chi2 = 9.333, P = 0.002 vs pCI-neo) and 53.3% (8/15, chi2 = 6.651, P = 0.010 vs saline and chi2 = 10.311, P = 0.001 vs pCI-neo) respectively. The average tumor diameter of the pHCV-NS3-Th1 treated group was significantly smaller compared with the control groups and the pHCV-NS3 treated group (P =0.001). Moreover, the average survival time of tumor-bearing mice immunized with pHCV-NS3-Th1 was 6 days longer compared with the saline treated group, 12 days longer compared with the pCI-neo treated group (P =0.001), and 6 days compared with the pHCV-NS3 treated group.


CONCLUSIONS
HCV NS3 Th1 epitope vaccine might be a potential biotherapy candidate against HCV infection.
Gao
Ming
M
Beijing Institute of Transfusion Medicine, Beijing 100850, China.
Wang
Hai-ping
HP
Zhou
Yong
Y
Wang
Jia-jun
JJ
Wang
Yan-ning
YN
Wang
Quan-li
QL
D000818:Animals; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009368:Neoplasm Transplantation; D011897:Random Allocation; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000627:therapeutic use*; D014761:Viral Hepatitis Vaccines / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis* / Q000235:genetics; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases