Preliminary observation on antitumor effect of HPV58 composite DNA vaccine / 中华妇产科杂志

ABSTRACT

Objective To initially observe the antitumor immune of PVAX1-HPV58mE6E7FcGB composite DNA vaccine.Methods Before detecting immune effect of the vaccine,the B16-HPV58E6E7 tumor cell line was built which could steadily express HPV58E6E7 fusion gene.Then,HPV58E6E7-GST fusion protein as an antigen was expressed and purified.Before or after immunized with the vaccine,the C57BL/6 mice were challenged by B16-HPV58E6E7 cells.Anti-tumor transplantation and tumor growth inhibition experiment were performed to observe prevention and treatment effects on the vaccine.Specific humoral and cellular immune responses in the immunized mice were detected by ELISA,enzyme linked immunospot assay (ELISPOT) and cytotoxic T lymphocyte (CTL) method.Results In the anti-tumor transplantation experiment,tumor formation rate was only 9/15 in the mice which were immunized by PVAX1-HPV58mE6E7FcGB vaccine,time before tumor formation was the longest [(13.6 ± 1.7) days] and tumor growth was the slowest in the vaccine group.In tumor growth inhibition experiment,inhibition rate reached 81.4％ in the vaccine group.Except tumor formation rate,all data in the vaccine group was superior to the pure antigen PVAX1-HPV58mE6E7Fc group (P ＜ 0.05).Humoral immune effect showed that both the vaccine and the pure antigen could induce specific antibody in the immunized mice,and the highest titer were 1 ∶ 25600 and 1 ∶ 12800,respectively.Although there was not significant difference of antibody titer between the vaccine and the pure antigen group (P ＞ 0.05),the number of activated T cells in the vaccine group was almost four times as that in the pure antigen group [(219 ±34)/4 × 105 spleen lymphocytes versus (55 ±25)/4 × 105 spleen lymphocytes,P ＜ 0.05],and the highest specific CTL that vaccine induced was significantly higher than that of pure antigen (43.3％ versus 31.3％,P ＜ 0.05).Conclusions Humoral and cellular immune response could be effectively stimulated by PVAX1-HPV58mE6E7FcGB composite DNA vaccine.Growth of B16-HPV58E6E7 cells was significantly inhibited in the immunized mice.The cellular immune effect on the vaccine was superior to the pure antigen.Therefore,PVAX1-HPV58mE6E7FcGB could be used as a candidate vaccine for immune therapy to the HPV58 positive tumors and precancerous lesions.