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

Clin Vaccine Immunol. 2009 Apr;16(4):499-505. doi: 10.1128/CVI.00471-08. Epub 2009 Feb 18.

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gamma interferon T-cell response after three immunizations and lower plasma vRNA levels for 6 weeks after ART was withdrawn compared to the saline-treated animal group.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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives
  • 2,2'-Dipyridyl / pharmacology
  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Disinfectants / pharmacology
  • Disulfides / pharmacology
  • HIV Antibodies / blood*
  • Interferon-gamma / metabolism
  • Macaca mulatta
  • Oligodeoxyribonucleotides / administration & dosage*
  • Oligodeoxyribonucleotides / pharmacology
  • RNA, Viral / blood
  • SAIDS Vaccines / immunology*
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Immunodeficiency Virus / immunology*
  • T-Lymphocytes / immunology
  • Viral Load
  • Virus Inactivation*

Substances

  • Adjuvants, Immunologic
  • Anti-HIV Agents
  • CPG-oligonucleotide
  • Disinfectants
  • Disulfides
  • HIV Antibodies
  • Oligodeoxyribonucleotides
  • RNA, Viral
  • SAIDS Vaccines
  • 2,2'-dipyridyl disulfide
  • 2,2'-Dipyridyl
  • Interferon-gamma