[Study of immune responses induced by human papillomavirus type 18 L1-E6 and L1-E7 chimeric gene DNA vaccines in mice].
OBJECTIVE
To examine the humoral and cellular immunoresponses induced by HPV18 L1-E6 and L1-E7 chimeric gene DNA vaccines in mice.


METHODS
54 BALB/c mice were divided into 9 groups randomly, and then vaccinated with various recombinant plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immune adjuvants (pLXHDmB7-2 or LTB) through different administration routes (intramuscular or intranasal). After the third inoculation, blood samples were taken to measure specific antibody, and footpad swelling test was used to detect delayed-type hypersensitivity(DTH). Mice were killed and spleens were taken to prepare single spleen cell suspension for lymphocyte proliferation assay and CD4(+)/CD8(+), IFN-gamma(+) or IL-4(+) T cells double staining FACS assay. And then the pathological changes of the swollen footpad were observed.


RESULTS
Compared with control, significant immunoresponses were observed in different experimental groups. The level of specific serum IgG against HPV in experiment groups was much higher than that of control group, and intramuscular immunization group had the highest antibody level. The footpad from immunized mice injected with virus-like particles was swollen and harden, and a large amounts of mononuclear cells can be seen in the footpad tissues. Intramuscular immunization groups were superior to intranasal immunization groups in DTH response, splenocyte proliferation and CD8(+) IFN-gamma(+) cell number, while CD4(+) IL-4(+) cell number was higher in intranasal immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were superior to other groups in immune responses.


CONCLUSIONS
The recombinant plasmids could induce strong humoral and cellular immunoresponses in mice. Costimulatory molecule B7-2 could enhance the immune responses against HPV18 induced by the L1-E6 and L1-E7 DNA vaccines when used as an adjuvant.
Li
Ang
A
Institute for Cancer Research, School of Life Sciences and Technology College, Xi'an Jiaotong Univeisity, Xi'an 710061, China.
Yang
Jin
J
Lai
Bao-chang
BC
Geng
Yi-ping
YP
Wang
Yan
Y
Wang
Yi-li
YL
D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D052161:Human papillomavirus 18 / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053918:Papillomavirus Vaccines; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D019444:Vaccines, DNA / Q000276:immunology*; D014764:Viral Proteins; D014765:Viral Vaccines / Q000276:immunology*
D036022:Capsid Proteins; D007074:Immunoglobulin G; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma; C480565:L1 protein, Human papillomavirus type 18