[Enhancement of human papillomavirus type 16E6E7 vaccine-induced specific immune response by coimmunization with B7-1 co-stimulatory gene].
OBJECTIVE
To develop a therapeutic vaccine against human tumors associated with human papillomavirus type 16E6E7 (HPV16E6E7) which is modified from a Chinese patient of the cervical cancer which possessing the antigenicity and no transforming activity, and explore more active vaccine for inducing cellular immunity with mouse co-stimulatory molecular B7-1 gene.


METHODS
The modified E6E7 gene expression plasmid pVR1012-fmE6E7 was constructed and transfected Cos-7 cells, and the E7 protein specific expression was testified by immunofluorescence assay. C57BL/6 mice were immunized intramuscularly with pVR1012-fmE6E7 alone or in combination with B7-1 gene expression plasmid (pcDNA3.1-B7-1). The activity of cytotoxic T lymphocytes (CTLs) was analyzed with 51Cr specific release assay and the specific antibody in sera was analyzed by indirect ELISA. HPV16 positive C57BL/6 tumor cells C3 were inoculated subcutaneously in the vaccinated mice to assay the growth of transplanted tumors.


RESULTS
The specific CTLs and antibody from immunized mice were induced efficaciously by the E6E7 gene immunization, and co-administration of B7-1 gene could significantly enhanced the CTLs immune responses of fmE6E7, and protected 33% immunized mice against C3 tumor cells challenge. In contrast, all the mice immunized only with fmE6E7 gene developed transplanted tumors after C3 cells challenge. There was no difference in E7 specific antibody responses between mice immunized with the E6E7 gene only and co-administration with B7-1 gene.


CONCLUSIONS
The modified E6E7 gene can be used as target gene for developing DNA vaccine, and B7-1 gene may represent an attractive adjuvant for enhancement of the specific cellular immune responses.
Xu
Xue-mei
XM
Department of Biophysics, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China.
Zhu
Ming-zhao
MZ
Zhang
Ming-ce
MC
Si
Jing-yi
JY
Li
Kun
K
Song
Guo-xing
GX
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019444:Vaccines, DNA / Q000276:immunology*
D000912:Antibodies, Neoplasm; D018122:B7-1 Antigen; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16