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Journal of Virology, June 2002, p. 6138-6146, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6138-6146.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Critical Role for Env as well as Gag-Pol in Control of a Simian-Human Immunodeficiency Virus 89.6P Challenge by a DNA Prime/Recombinant Modified Vaccinia Virus Ankara Vaccine

Rama Rao Amara,1,2,3 James M. Smith,1,2,3 Silvija I. Staprans,3,4 David C. Montefiori,5 Francois Villinger,1,6 John D. Altman,1,3 Shawn P. O'Neil,1,2,3 Natalia L. Kozyr,1,4 Yan Xu,1,2 Linda S. Wyatt,7 Patricia L. Earl,7 James G. Herndon,2 Janet M. McNicholl,8 Harold M. McClure,1,2 Bernard Moss,7 and Harriet L. Robinson1,2,3*

Vaccine Research Center,1 Yerkes Regional Primate Research Center,,2 Departments of Pathology and Laboratory Medicine,,6 Microbiology and Immunology,3 Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322,4 Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710,5 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,7 Division of AIDS, STD and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 303308

Received 8 January 2002/ Accepted 22 March 2002

Cellular immune responses against epitopes in conserved Gag and Pol sequences of human immunodeficiency virus type 1 have become popular targets for candidate AIDS vaccines. Recently, we used a simian-human immunodeficiency virus model (SHIV 89.6P) with macaques to demonstrate the control of a pathogenic mucosal challenge by priming with Gag-Pol-Env-expressing DNA and boosting with Gag-Pol-Env-expressing recombinant modified vaccinia virus Ankara (rMVA). Here we tested Gag-Pol DNA priming and Gag-Pol rMVA boosting to evaluate the contribution of anti-Env immune responses to viral control. The Gag-Pol vaccine raised frequencies of Gag-specific T cells similar to those raised by the Gag-Pol-Env vaccine. Following challenge, these rapidly expanded to counter the challenge infection. Despite this, the control of the SHIV 89.6P challenge was delayed and inconsistent in the Gag-Pol-vaccinated group and all of the animals underwent severe and, in most cases, sustained loss of CD4+ cells. Interestingly, most of the CD4+ cells that were lost in the Gag-Pol-vaccinated group were uninfected cells. We suggest that the rapid appearance of binding antibody for Env in Gag-Pol-Env-vaccinated animals helped protect uninfected CD4+ cells from Env-induced apoptosis. Our results highlight the importance of immune responses to Env, as well as to Gag-Pol, in the control of immunodeficiency virus challenges and the protection of CD4+ cells.

* Corresponding author. Mailing address: 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, June 2002, p. 6138-6146, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6138-6146.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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