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Journal of Virology, December 2003, p. 12980-12985, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.12980-12985.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Varied Immunity Generated in Mice by DNA Vaccines with Large and Small Hepatitis Delta Antigens

Yi-Hsiang Huang,1,2 Jaw-Ching Wu,1,2* Sheng-Chieh Hsu,3 and Wan-Jr Syu3

Institute of Clinical Medicine,1 Institute of Microbiology and Immunology, School of Medicine, National Yang-Ming University,3 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China2

Received 4 June 2003/ Accepted 5 September 2003

Whether the hepatitis delta virus (HDV) DNA vaccine can induce anti-HDV antibodies has been debatable. The role of the isoprenylated motif of hepatitis delta antigens (HDAg) in the generation of immune responses following DNA-based immunization has never been studied. Plasmids p2577L, encoding large HDAg (L-HDAg), p2577S, expressing small HDAg (S-HDAg), and p25L-211S, encoding a mutant form of L-HDAg with a cysteine-to-serine mutation at codon 211, were constructed in this study. Mice were intramuscularly injected with the plasmids. The anti-HDV antibody titers, T-cell proliferation responses, T-helper responses, and HDV-specific, gamma interferon (IFN-{gamma})-producing CD8+ T cells were analyzed. Animals immunized with p2577S showed a strong anti-HDV antibody response. Conversely, only a low titer of anti-HDV antibodies was detected in mice immunized with p2577L. Epitope mapping revealed that the anti-HDV antibodies generated by p2577L vaccination hardly reacted with epitope amino acids 174 to 194, located at the C terminus of S-HDAg. All of the HDAg-encoding plasmids could induce significant T-cell proliferation responses and generate Th1 responses and HDV-specific, IFN-{gamma}-producing CD8+ T cells. In conclusion, HDAg-specific antibodies definitely exist following DNA vaccination. The magnitudes of the humoral immune responses generated by L-HDAg- and S-HDAg-encoding DNA vaccines are different. The isoprenylated motif can mask epitope amino acids 174 to 195 of HDAg but does not interfere with cellular immunity following DNA-based immunization. These findings are important for the choice of a candidate HDV DNA vaccine in the future.

* Corresponding author. Mailing address: Institute of Clinical Medicine, National Yang-Ming University, and Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, 201 Shih-Pai Rd., Sec. 2, Taipei 112, Taiwan. Phone: 886-2-28712121, ext. 3218. Fax: 886-2-28749437. E-mail: jcwu{at}vghtpe.gov.tw.

Journal of Virology, December 2003, p. 12980-12985, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.12980-12985.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, S.-Y., Wu, J.-C., Chiang, T.-Y., Huang, Y.-H., Su, C.-W., Sheen, I-J. (2007). Positive Selection of Hepatitis Delta Antigen in Chronic Hepatitis D Patients. J. Virol. 81: 4438-4444 [Abstract] [Full Text]  
  • Huang, Y.-H., Tao, M.-H., Hu, C.-p., Syu, W.-J., Wu, J.-C. (2004). Identification of novel HLA-A*0201-restricted CD8+ T-cell epitopes on hepatitis delta virus. J. Gen. Virol. 85: 3089-3098 [Abstract] [Full Text]  
  • Karayiannis, P., Main, J., Thomas, H. C. (2004). Hepatitis vaccines. Br Med Bull 70: 29-49 [Full Text]  


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