Coimmunization with IL-15 plasmid enhances the longevity of CD8 T cells induced by DNA encoding hepatitis B virus core antigen.
OBJECTIVE
To test the feasibility of delivering a plasmid encoding IL-15 as a DNA vaccine adjuvant for improving the immune responses induced by hepatitis B virus core gene DNA vaccine.


METHODS
We used RT-PCR based strategies to develop IL-15 expression constructs. We first confirmed that the gene could be expressed in Escherichia coli due to the poor expression of IL-15. Then the bioactivity of IL-15 plasmid expression product was identified by CTLL-2 proliferation assay. One hundred micrograms of DNA from each of the IL-15 eukaryotic expressed plasmid and the recombinant plasmid harboring DNA encoding the 144 amino acids of the N-terminus of HBV core gene (abbreviated pHBc144) was used to co-immunize C57 BL/6 mice. The titer of anti-HBcIgG was detected by ELISA and the antigen-specific CD8(+) T cells (CD8(+)IFN-gamma(+) T cells) were detected by intracellular cytokine staining at different time points.


RESULTS
After co-immunization by pIL-15 and pHBc144 DNA vaccine the antigen-specific CD8(+) cells of mice increased gradually, the first peak of immune response appeared 14 d later, then the number of antigen-specific CD8(+) Ts cells decreased gradually and maintained at a steady level in 3 mo. After boosting, the number of antigen-specific CD8(+) T cells reached the second peak 10 d later with a double of the 1st peak, then the number of antigen-specific CD8(+) T cells decreased slowly. IL-15 as a gene adjuvant had no significant effect on humoral immune responses induced by hepatitis B virus core gene DNA vaccine, but increased the memory antigen-specific CD8(+) T cells induced by hepatitis B virus core gene DNA vaccine.


CONCLUSIONS
DNA vaccine constructed by HBc Ag 1-144 amino acid induces effective cell immunity, and cytokine plasmid-delivered IL-15 enhances the longevity of CD8(+) T cells.
Zhang
Wei
W
Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Dong
Sheng-Fu
SF
Sun
Shu-Hui
SH
Wang
Yuan
Y
Li
Guang-Di
GD
Qu
Di
D
D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004279:DNA, Viral / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism; D005260:Female; D015967:Gene Expression Regulation, Viral; D006509:Hepatitis B / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D017325:Hepatitis B Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D007156:Immunologic Memory / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D019409:Interleukin-15; D019444:Vaccines, DNA