3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

CONTROL OF VIREMIA AFTER ANTIRETROVIRAL TREATMENT AND THERAPEUTIC VACCINATION WITH NOVEL FORMS OF DNA VACCINES IN CHRONICALLY SIVMAC251-INFECTED MACAQUES

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuOa0101

Felber B.¹, von Gegerfelt A.¹, Rosati M.¹, Alicea C.¹, Roth P.¹, Bear J.¹, Valentin A.¹, Boyer J.², Weiner D.³, Bischofberger N.⁴, Markham P.⁵, Albert P.⁶, Franchini G.⁶, Pavlakis G.^1
1NCI, Frederick, United States of America, ²U. of Pennsylvania, Pensylvania, United States of America, ³U. of Pennsylvania, Philadelphia, United States of America, ⁴Gilead, Foster City, United States of America, ⁵ABL, Inc., Kensington, United States of America, ⁶NCI, Bethesda, United States of America

INTRODUCTION: We explored therapeutic immunization of ART-treated SIVmac251 infected rhesus macaques, using a new generation of optimized DNA-based vaccine vectors that produce either secreted or intracellularly degraded antigens.

METHODS: Macaques infected for 15-70 weeks with SIVmac251 were treated with a combination of 3 drugs (PMPA, ddl and Stavudine) for 12-23 weeks. During this time, the animals were vaccinated via intramuscular route with optimized forms of DNA vectors expressing SIV antigens and then released from treatment. The animals were monitored for rebounding virus and changes in SIV specific immune responses during and after termination of therapy. Statistical analyses were performed for all the animals at least partially responding to ART by reducing viremia.

RESULTS: Macaques receiving DNA showed a significant decrease in viral load after therapy termination compared to controls (p<0.001, Wilcoxon rank sum test). We found that 6 of 12 ART-treated and vaccinated animals had substantial decreases in virus loads for long periods, and reached levels below the detection of the virus load assay. Three additional animals had substantial reductions in viremia after ART and immunotherapy. Analysis of 11 animals that received only ART showed that none controlled viremia fully after release from ART. Therefore, DNA vaccination but not ART alone led to substantial decreases in viremia. Measurement of cellular immune responses showed induction of SIV-specific cellular immune responses during therapy. The animals controlling viremia had persistent cellular immune responses after release from ART. Some animals continue to control viremia levels after 2 years.

CONCLUSIONS: The combination of novel forms of DNA vaccines administered during ART treatment induced an immune response able to control viremia after removal of ART. Importantly, animals able to control virus maintained this ability for two years after ART termination. Optimized DNA vectors may be beneficial either alone or in combination with other vaccine modalities as an addition to antiretroviral treatment.

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050724
Basic | TuOa0101 | Gn Pavlakis
13.2 489 13.2 Therapeutic vaccination, HIV vaccine development trials

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