Long term infection with bovine leukaemia virus structural gene vector acts as a protective DNA vaccine against AIDS-like BLV disease in rabbits
aCancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia, bCentre of Excellence MOLECULAR MEDICINE of the SAS Bratislava, Slovakia, OH, United States, cCenter for Retrovirus Research, dDepartment of Veterinary Biosciences and Molecular Virology, eImmunology & Medical Genetics, fComprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
AIM A prototypic vaccination approach to prevent disease caused by more complex retroviruses was tested. Rabbit BLV model was used to test whether simplified replication-competent bovine leukemia virus structural gene vector virus - BLV SGV (J. Virol. 71:1514-1520, 1997) can be used as a DNA preventive vaccine. Previously we have shown BLV SGV that lack tax, rex, RIII, and GIV, and the cis-acting Tax and Rex response elements is able to infect rabbits, induce virus immunological response without pathogenicity, while wild type BLV caused AIDS-like symptoms leading to death of the rabbits due to opportunistic infections. (AIDS 3:775-780 1989; J. Virol. 73:8160-8166, 1999). BLV SGV vaccinated and control rabbits were challenged with different amounts wild type virus producing cells at different period of time after DNA vaccination. METHODS Virus infection, pathogenicity, and immunogenicity were monitored by analysis of provirus DNA and presence of tax gene with PCR and Southern blot hybridization, and by seroconversion to BLV structural protein with Western blot. RESULTS Chinchilla rabbits two years after vaccination with BLV SGV were found resistant to high dose virus challenge. They were challenged once more again two years after the first challenge. No pathologic signs were noticed up to four and half year observation period in one of the challenged animal. The similar dose of virus caused death of not vaccinated rabbit. Rabbits transfused intravenously with blood from vaccinated animals were partially protected against challenge. CONCLUSIONS The results are consistent with the working hypothesis that simplified more complex retrovirus might be used as DNA vaccine preventing pathologic effects of more complex retroviruses. The data imply that SGV based on HTLV or HIV is a promising approach against lymphotropic disease by human retroviruses.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 791 (Viral Infections).