Therapeutic immunization of HIV-infected chimpanzees using HIV-1 plasmid antigens and interleukin-12 expressing plasmids

Objective: To assess HIV-1 DNA vaccination and co-immunization with interle ukin (IL)-12 and IL-10 as immunotherapy in the HIV-1 infected chimpanzee mo del system. Methods: Four chimpanzees that were infected with HIV-1-IIIB for longer tha n 4 years and remained symptom free were immunized with HIV-1 plasmid vacci nes. Two chimpanzees were immunized with DNA plasm ids that encoded env/rev , gag/pol along with a plasmid that: encoded both chains of human IL-12. A third animal was immunized with HIV-1 DNA vaccine constructs and co-immuniz ed with an IL-10 expressing plasmid. Finally a control animal received the HIV-1 DNA vaccine constructs alone. Results: There was no evidence of systemic toxicity associated with the adm inistration of the DNA vaccines or the cytokine-expressing plasmids. We obs erved that the IL-12/ HIV-1 DNA vaccinated animals had enhanced proliferati ve responses to multiple HIV-1 antigens at multiple time points. The animal that was co-immunized with HIV-1 and IL-10 did not have any changes in the proliferative responses. Finally, the control chimpanzee demonstrated mode rate increases in the proliferative responses to HIV-1 antigens. The animal that received HIV-1 vaccines alone and the animals co-immunized with IL-12 all had declines in viral load over the course of the study, however, the decrease in viral loads were transient in all animals. Conclusion: Immunization of HIV-1 infected chimpanzees with DNA based vacci nes containing the env, gag and pol genes can transiently boost the env spe cific proliferative responses. Co-administration of IL-12 expressing plasmi ds further leads to transient boosting of the proliferative response to the core protein, p24 as well. However, at these doses the impact on viral loa d is minimal. (C) 2000 Lippincott Williams & Wilkins.