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Journal of Virology, June 2006, p. 5875-5885, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.00171-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

Nancy A. Wilson,1* Jason Reed,1 Gnankang S. Napoe,1 Shari Piaskowski,2 Andy Szymanski,2 Jessica Furlott,1 Edna J. Gonzalez,2 Levi J. Yant,1 Nicholas J. Maness,1 Gemma E. May,1 Taeko Soma,1 Matthew R. Reynolds,1 Eva Rakasz,1 Richard Rudersdorf,1 Adrian B. McDermott,2,{dagger} David H. O'Connor,2 Thomas C. Friedrich,1 David B. Allison,3 Amit Patki,3 Louis J. Picker,4 Dennis R. Burton,5 Jing Lin,6 Lingyi Huang,6 Deepa Patel,6 Gwendolyn Heindecker,6 Jiang Fan,6 Michael Citron,6 Melanie Horton,6 Fubao Wang,6 Xiaoping Liang,6 John W. Shiver,6 Danilo R. Casimiro,6 and David I. Watkins1,2*

Wisconsin National Primate Research Center, University of Wisconsin—Madison, Madison, Wisconsin 53711,1 Department of Pathology and Lab Medicine, University of Wisconsin—Madison, Madison, Wisconsin,2 Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama 35294,3 Vaccine and Gene Therapy Institute, Department of Pathology and Department of Molecular Microbiology and Immunology, and the Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006,4 Departments of Immunology and Molecular Biology, Scripps Research Institute, La Jolla, California 92037,5 Merck Research Labs, West Point, Pennsylvania 194866

Received 25 January 2006/ Accepted 22 March 2006

The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4+ memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.


* Corresponding author. Mailing address: University of Wisconsin—Madison, 555 Science Drive, Madison, WI 53711. Phone for Nancy A. Wilson: (608) 263-5953. Fax: (608) 265-8084. E-mail: nwilson{at}primate.wisc.edu. Phone for David I. Watkins: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu.

{dagger} Present address: IAVI, New York, NY 10038.


Journal of Virology, June 2006, p. 5875-5885, Vol. 80, No. 12
0022-538X/06/$08.00+0     doi:10.1128/JVI.00171-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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