Attempted therapeutic immunization in a chimpanzee chronic HBV carrier with a high viral load

• Published in: Journal of medical primatology Vol. 35; no. 3; pp. 165 - 171
• Main Authors: Shata, Mohamed Tarek M., Pfahler, Wolfram, Brotman, Betsy, Lee, Dong-Hun, Tricoche, Nancy, Murthy, Krishna, Prince, Alfred M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2006
• Subjects: Animals; Antibody Affinity - immunology; Antiviral Agents - therapeutic use; Ape Diseases - immunology; Ape Diseases - therapy; Ape Diseases - virology; Canarypox virus; chimpanzee studies; DNA, Viral - chemistry; DNA, Viral - genetics; Female; Hepatitis B Core Antigens - immunology; Hepatitis B Surface Antigens - genetics; Hepatitis B Surface Antigens - immunology; Hepatitis B Vaccines - immunology; Hepatitis B Vaccines - therapeutic use; Hepatitis B virus; Hepatitis B virus - immunology; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - therapy; Hepatitis B, Chronic - veterinary; Hepatitis B, Chronic - virology; Immunization - methods; Immunization - veterinary; immunotherapy; Interferon-gamma - blood; lamivudine; Lamivudine - therapeutic use; Pan troglodytes; Protein Precursors - genetics; Protein Precursors - immunology; RNA, Viral - blood; Vaccines, DNA - immunology; Vaccines, DNA - therapeutic use; Vaccinia virus; Viral Load
• ISSN: 0047-2565; 1600-0684
• DOI: 10.1111/j.1600-0684.2006.00152.x

Background  We previously reported successful therapeutic immunization in a chimpanzee having a relatively low viral load, which was immunized with recombinant plasmid hepatitis B surface antigen (HBsAg) DNA and boosted with recombinant HBsAg encoding canarypox virus. In the present study, we attempted to confirm these findings in an animal with a high virus load. Methods and Results  We tested three immunization strategies successively over a 3‐year period. In the first of these, we administered four monthly injections of DNA encoding HBsAg + PreS2 + hepatitis B core antigen (HBcAg) + DNA encoding interleukin (IL)‐12, (given 3 days later), and boosted with canarypox expressing all of the above HBV genes 6 months after initial immunization. No reduction in viral load was observed. In the second trial, we administered lamivudine for 8 weeks, and then began monthly DNA‐based immunization with plasmids expressing the above viral genes; however, viral loads rebounded 1 week after termination of lamivudine therapy. In a third trial, we continued lamivudine therapy for 30 weeks and immunized with vaccinia virus expressing the above viral genes 18 and 23 weeks after the start of lamivudine therapy. Again viral loads rebounded shortly after cessation of lamivudine treatment. Analysis of cell‐mediated immune responses, and their avidity, revealed that DNA‐based immunization produced the strongest enhancement of high avidity T‐cell responses, while recombinant vaccinia immunization during lamivudine therapy enhanced low avidity responses only. The strongest low and high avidity responses were directed to the middle surface antigen. Conclusions  Three strategies for therapeutic immunization failed to control HBV viremia in a chronically infected chimpanzee with a high viral load.