DNA immunization in combination with effective antiretroviral drug therapy controls viral rebound and prevents simian AIDS after treatment is discontinued.
DNA immunization in conjunction with antiretroviral therapy was evaluated in SIV-infected rhesus macaques treated with [R]-9-[2-phosphonylmethoxypropyl]adenine (PMPA). Macaques were immunized monthly with DNA vaccines expressing either SIV gag/tat or SIV gag/tat and 19 CD8+ T cell epitopes during 7 months of therapy. Half the animals from each group were additionally immunized before infection. Only 60% of the animals (4 controls, 20 vaccinated) responded to PMPA (ART responders). All 4 ART responder controls demonstrated viral rebound or CD4 decline after PMPA was withdrawn. In contrast, 17 of 20 vaccinated ART responders contained viral rebound for over 7 months after PMPA was withdrawn. Viral control correlated with stable CD4 counts, higher lymphoproliferation and an increase in the magnitude and breadth of the CD8+ T cell response. Immunizing before infection or with multi-epitopes enhanced these effects. These results demonstrate that DNA immunization during antiretroviral therapy may be an effective strategy to treat HIV infection.
Fuller
Deborah Heydenburg
DH
PowderJect Vaccines, Inc., Middleton, WI 53562, USA. dfuller@pitt.edu
Rajakumar
Premeela A
PA
Wu
Mary S
MS
McMahon
Christopher W
CW
Shipley
Tim
T
Fuller
James T
JT
Bazmi
Afrouz
A
Trichel
Anita M
AM
Allen
Todd M
TM
Mothe
Bianca
B
Haynes
Joel R
JR
Watkins
David I
DI
Murphey-Corb
Michael
M
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods; D008253:Macaca mulatta; D063065:Organophosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*; D013223:Statistics as Topic; D000068698:Tenofovir; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014766:Viremia / Q000517:prevention & control*; D028761:Withholding Treatment
D019380:Anti-HIV Agents; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015696:Gene Products, tat; D063065:Organophosphonates; D012367:RNA, Viral; D019444:Vaccines, DNA; D000068698:Tenofovir; D000225:Adenine