title: Enhanced antibody responses elicited by a CpG adjuvant do not improve the protective effect of an aldrithiol-2-inactivated simian immunodeficiency virus therapeutic AIDS vaccine.
abstract: The potential benefit of using unmethylated CpG oligoribodeoxynucleotides (ODN) as an adjuvant in a therapeutic simian immunodeficiency virus (SIV) vaccine consisting of AT2-inactivated SIVmac239 was evaluated in SIV-infected rhesus macaques receiving antiretroviral therapy (ART). We hypothesized that using CpG ODN as an adjuvant in therapeutic vaccination would enhance SIV-specific immune responses and suppress SIV replication after ART was stopped. To test our hypothesis, we immunized chronically SIV-infected rhesus macaques receiving ART with one of the following therapeutic vaccines: (i) AT2-inactivated SIVmac239, (ii) CpG10103 plus AT2-inactivated SIVmac239, (iii) CpG10103, and (iv) saline. While immunization with CpG plus AT2-SIVmac239 significantly increased SIV-specific immunoglobulin G (IgG) antibody titers, the mean plasma viral RNA (vRNA) level in these animals after ART did not differ from those of saline-treated animals. The AT2-inactivated SIVmac239-immunized animal group had a significantly higher mean SIV-specific gamma interferon T-cell response after three immunizations and lower plasma vRNA levels for 6 weeks after ART was withdrawn compared to the saline-treated animal group. Compared to the saline control group, the animal group treated with CpG alone had a significantly higher mean SIV-specific lymphocyte proliferation index and a higher rate of plasma vRNA rebound after ART. These results demonstrate that while the use of CpG as an adjuvant enhances SIV-specific antibody responses, this does not improve the control of SIV replication after ART is stopped. The lack of benefit may be related to the high levels of SIV-specific lymphocyte proliferation in the CpG adjuvant group.
authors.affiliation: Center for Comparative Medicine, University of California, Davis, 95616, USA.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Blozis
authors.forename: Michael
authors.initials: M
authors.lastname: Lederman
authors.forename: Arthur
authors.initials: A
authors.lastname: Krieg
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004202:Disinfectants / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology; D015483:HIV Antibodies / Q000097:blood*; D007371:Interferon-gamma / Q000378:metabolism; D008253:Macaca mulatta; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load; D038301:Virus Inactivation
chemical_list: D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; C408982:CPG-oligonucleotide; D004202:Disinfectants; D004220:Disulfides; D015483:HIV Antibodies; D009838:Oligodeoxyribonucleotides; D012367:RNA, Viral; D018449:SAIDS Vaccines; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; D007371:Interferon-gamma