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Clinical and Vaccine Immunology, April 2009, p. 499-505, Vol. 16, No. 4
1071-412X/09/$08.00+0     doi:10.1128/CVI.00471-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Yichuan Wang,1,2 Shelley A. Blozis,3 Michael Lederman,4 Arthur Krieg,5 Alan Landay,6 and Christopher J. Miller1,2*

Center for Comparative Medicine,1 California National Primate Research Center,2 Department of Psychology, University of California, Davis, Davis, California 95616,3 Center for AIDS Research, Case Western Reserve University, University Hospitals/Case Medical Center, Cleveland, Ohio,4 Coley Pharmaceutical Group, Wellesley, Massachusetts 02481,5 Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois6

Received 14 December 2008/ Returned for modification 14 January 2009/ Accepted 8 February 2009

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gamma interferon T-cell response after three immunizations and lower plasma vRNA levels for 6 weeks after ART was withdrawn compared to the saline-treated animal group.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

* Corresponding author. Mailing address: CNPRC, UC Davis, One Shields Ave., Davis, CA 95616. Phone: (530) 752-0447. Fax: (530) 754-4411. E-mail: cjmiller{at}ucdavis.edu

{triangledown} Published ahead of print on 18 February 2009.

Clinical and Vaccine Immunology, April 2009, p. 499-505, Vol. 16, No. 4
1071-412X/09/$08.00+0     doi:10.1128/CVI.00471-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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