Analysis of humoral immunity of hepatitis D virus DNA vaccine generated in mice by using different dosage, gene gun immunization, and in vivo electroporation.
BACKGROUND
Hepatitis D virus (HDV) DNA vaccine can produce Th1 and cytotoxic T-cell immune responses but only a low anti-HDV antibody titer is generated with a large hepatitis D antigen (L-HDAg) construct. In contrast, DNA vaccine expressing small hepatitis D antigen (S-HDAg) can generate a high titer of anti-HDV antibodies. Whether the low humoral immunity of L-HDAg DNA vaccine is due to inadequate dosage or can be ameliorated by other modes of immunization needs further evaluation.


METHODS
Plasmid (p25L) encoding L-HDAg and plasmid (pS/p25L) coexpressing hepatitis B surface antigen (HBsAg) and L-HDAg were used in this study. We compared the humoral response generated in mice using different plasmid DNA dosages and modes of immunization, including gene gun and in vivo electroporation (EP).


RESULTS
Intramuscular injection with a high dose of plasmid DNA (10 mg/kg) produced strong antibodies to HBsAg earlier than the usual dose did, but did not augment the anti-HDV response. Gene gun DNA immunization could not provide a better humoral immune response to HDV. EP DNA immunization had a higher anti-HDV seroconversion rate of 80%, but the anti-HDV antibody responses were generally weak (titer < or = 400:1).


CONCLUSIONS
The low humoral immunogenicity of DNA vaccine with L-HDAg cannot be ameliorated by different dosage, gene gun immunization, or in vivo EP intramuscular injection. DNA vaccine with a L-HDAg construct may not be a candidate HDV vaccine to generate anti-HDV humoral immunity.
Shiau
Yih-Tsong
YT
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan, ROC.
Huang
Yi-Hsiang
YH
Wu
Jaw-Ching
JC
Tao
Mi-Hua
MH
Syu
Wan-
W
Chang
Full-Young
FY
Lee
Shou-Dong
SD
D000818:Animals; D019470:Biolistics; D018274:Electroporation; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood*; D003698:Hepatitis Delta Virus / Q000276:immunology*; D035923:Hepatitis delta Antigens / Q000235:genetics* / Q000276:immunology; D007114:Immunization; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D006508:Hepatitis Antibodies; D035923:Hepatitis delta Antigens; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines