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 interleukin (IL)-12 and IL-10 as immunotherapy in the HIV-1 infected chimpanzee model system.


METHODS
Four chimpanzees that were infected with HIV-1-IIIB for longer than 4 years and remained symptom free were immunized with HIV-1 plasmid vaccines. Two chimpanzees were immunized with DNA plasmids 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-immunized 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 administration of the DNA vaccines or the cytokine-expressing plasmids. We observed that the IL-12/HIV-1 DNA vaccinated animals had enhanced proliferative 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 moderate 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.


CONCLUSIONS
Immunization of HIV-1 infected chimpanzees with DNA based vaccines containing the env, gag and pol genes can transiently boost the env specific proliferative responses. Co-administration of IL-12 expressing plasmids further leads to transient boosting of the proliferative response to the core protein, p24 as well. However, at these doses the impact on viral load is minimal.
Boyer
J D
JD
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA. boyerj@mail.med.upenn.edu
Cohen
A D
AD
Ugen
K E
KE
Edgeworth
R L
RL
Bennett
M
M
Shah
A
A
Schumann
K
K
Nath
B
B
Javadian
A
A
Bagarazzi
M L
ML
Kim
J
J
Weiner
D B
DB
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D003257:Consumer Product Safety; D004279:DNA, Viral / Q000276:immunology*; D004195:Disease Models, Animal; D015752:Genes, env / Q000276:immunology; D015750:Genes, gag / Q000276:immunology; D015751:Genes, pol / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015488:HIV Antigens / Q000235:genetics* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D002679:Pan troglodytes; D010957:Plasmids / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology*; D019562:Viral Load
D016915:AIDS Vaccines; D004279:DNA, Viral; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA; D018664:Interleukin-12