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Journal of Virology, October 2002, p. 10147-10154, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10147-10154.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Slowly Declining Levels of Viral RNA and DNA in DNA/Recombinant Modified Vaccinia Virus Ankara-Vaccinated Macaques with Controlled Simian-Human Immunodeficiency Virus SHIV-89.6P Challenges

Yuyang Tang,1,2 Francois Villinger,1,3 Silvija I. Staprans,1,4 Rama Rao Amara,1,2,5 James M. Smith,1,2,5 James G. Herndon,2 and Harriet L. Robinson1,2,5*

Vaccine Research Center,1 Yerkes National Primate Research Center,2 Department of Pathology and Laboratory Medicine,3 Division of Infectious Diseases, Department of Medicine,4 Department of Microbiology and Immunology, Emory University Medical School, Emory University, Atlanta, Georgia 303295

Received 22 April 2002/ Accepted 28 June 2002

In a recent vaccine trial, we showed efficient control of a virulent simian-human immunodeficiency virus SHIV-89.6P challenge by priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env- expressing recombinant-modified vaccinia virus Ankara. Here we show that long-term control has been associated with slowly declining levels of viral RNA and DNA. In the vaccinated animals both viral DNA and RNA underwent an initial rapid decay, which was followed by a lower decay rate. Between 12 and 70 weeks postchallenge, the low decay rates have had half-lives of about 20 weeks for viral RNA in plasma and viral DNA in peripheral blood mononuclear cells and lymph nodes. In vaccinated animals the viral DNA has been mostly unintegrated and has appeared to be largely nonfunctional as evidenced by a poor ability to recover infectious virus in cocultivation assays, even after CD8 depletion. In contrast, in control animals, which have died, viral DNA was mostly integrated and a larger proportion appeared to be functional as evidenced by the recovery of infectious virus. Thus, to date, control of the challenge infection has appeared to improve with time, with the decay rates for viral DNA being at the lower end of values reported for patients on highly active antiretroviral therapy.

* Corresponding author. Mailing address: Yerkes National Primate Research Center, 954 Gatewood Rd., N.E., Atlanta, GA 30329. Phone: (404) 727-7217. Fax: (404) 727-7768. E-mail: hrobins{at}rmy.emory.edu.

Journal of Virology, October 2002, p. 10147-10154, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10147-10154.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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