CVI Accepts, published online ahead of print on 18 February 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00471-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The enhanced antibody responses elicited by a CpG adjuvant does not improve the protective effect of an AT-2 inactivated SIV therapeutic AIDS vaccine

Yichuan Wang, Shelley A. Blozis, Michael Lederman, Arthur Krieg, Alan Landay, and Christopher J. Miller^*

Center for Comparative Medicine, California National Primate Research Center, Department of Psychology, University of California, Davis, Davis, CA, 95616 USA; Center for AIDS Research, Case Western Reserve University, University Hospitals/Case Medical Center, Cleveland, Ohio, United States of America; Department of Immunology and Microbiology, Coley Pharmaceutical Group, Wellesley, MA 02481, USA; Rush University Medical Center, Chicago, IL, USA

^* To whom correspondence should be addressed. Email: cjmiller{at}ucdavis.edu.

The potential benefit of using unmethylated CpG-ODN as an adjuvant in a therapeutic SIV vaccine consisting of AT2-inactivated SIVmac239 was evaluated in SIV-infected rhesus macaques receiving anti-retroviral 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: 1) AT2-inactivated SIVmac239, 2) CpG10103+AT2 inactivated SIVmac239, 3) CpG10103 and 4) Saline. While CpG+AT2-SIVmac239 immunization significantly increased SIV-specific IgG antibody titers, the mean plasma viral RNA level in these animals after ART did not differ from saline treated animals. The AT2-inactivated SIVmac239 immunized animal group had a significantly higher mean SIV-specific IFN-gamma T cell response after 3 immunizations and lower plasma vRNA levels for 6 weeks after ART was withdrawn compared to the saline treated animal group. Compared to 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.