DNA-Based immunization produces Th1 immune responses to hepatitis delta virus in a mouse model.
Hepatitis delta virus (HDV) superinfection is one of the major causes of fulminant hepatitis in endemic areas of hepatitis B virus (HBV) infection. Currently, there is no effective treatment or vaccine against HDV superinfection. DNA-based immunization is a promising antiviral strategy to prevent or treat persistent viral infections. In this study, we investigated the immunological effects of DNA vaccines against HDV in BALB/c mice. Plasmid (pD) encoding large hepatitis D antigen (L-HDAg), or plasmid (pS/pD) coexpressing hepatitis B surface antigen (HBsAg) and L-HDAg, were injected into mice intramuscularly. The seroconversion rate, anti-HBs levels, anti-HDV titers, T-cell proliferation responses, and T-helper (Th)-release cytokine profiles were analyzed. Mice immunized with plasmids, pS/pD or pD, produced low, but significant, titers of anti-HDV antibodies. In contrast, pS/pD induced much stronger anti-HBs titers in the immunized animals. Interestingly, splenic lymphocytes derived from pS/pD-inoculated mice demonstrated significant proliferation responses to recombinant HBsAg and HDAg, and resulted in a Th1-like immune response as suggested by the production of interferon gamma (INF-gamma) and interleukin-2 (IL-2), but not IL-4. The splenic lymphocyte derived from the pD-inoculated mice showed a similar Th1 response to the stimulation of HDAg, but not to HBsAg. In conclusion, our results suggest that DNA vaccines against HDV can induce significant cellular immune responses with a Th1 preference. HBV and HDV coimmunization can be performed by DNA vaccines. These results are promising for the future development of prophylactic and therapeutic HDV vaccines.
Huang
Y H
YH
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
Wu
J C
JC
Tao
M H
MH
Syu
W J
WJ
Hsu
S C
SC
Chi
W K
WK
Chang
F Y
FY
Lee
S D
SD
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D003698:Hepatitis Delta Virus / Q000276:immunology*; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D016207:Cytokines; D006510:Hepatitis B Antibodies; D019444:Vaccines, DNA; D014765:Viral Vaccines