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Journal of Virology, December 2005, p. 15547-15555, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15547-15555.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Attenuation of Simian Immunodeficiency Virus SIVmac239 Infection by Prophylactic Immunization with DNA and Recombinant Adenoviral Vaccine Vectors Expressing Gag

Danilo R. Casimiro,1* Fubao Wang,1 William A. Schleif,1 Xiaoping Liang,1 Zhi-Qiang Zhang,1 Timothy W. Tobery,1 Mary-Ellen Davies,1 Adrian B. McDermott,1 David H. O'Connor,3 Arthur Fridman,2 Ansu Bagchi,2 Lynda G. Tussey,1 Andrew J. Bett,1 Adam C. Finnefrock,1 Tong-ming Fu,1 Aimin Tang,1 Keith A. Wilson,1 Minchun Chen,1 Helen C. Perry,1 Gwendolyn J. Heidecker,1 Daniel C. Freed,1 Anthony Carella,1 Kara S. Punt,1 Kara J. Sykes,1 Lingyi Huang,1 Virginia I. Ausensi,1 Margaret Bachinsky,1 Usha Sadasivan-Nair,1 David I. Watkins,3 Emilio A. Emini,1 and John W. Shiver1

Department of Vaccines and Biologics Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486,1 Applied Computer Sciences and Mathematics, Merck Research Laboratories, Merck & Co., Rahway, New Jersey 07065,2 Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin3

Received 14 April 2005/ Accepted 7 August 2005

The prophylactic efficacy of DNA and replication-incompetent adenovirus serotype 5 (Ad5) vaccine vectors expressing simian immunodeficiency virus (SIV) Gag was examined in rhesus macaques using an SIVmac239 challenge. Cohorts of either Mamu-A*01(+) or Mamu-A*01(–) macaques were immunized with a DNA prime-Ad5 boost regimen; for comparison, a third cohort consisting of Mamu-A*01(+) monkeys was immunized using the Ad5 vector alone for both prime and boost. All animals, along with unvaccinated control cohorts of Mamu-A*01(+) and Mamu-A*01(–) macaques, were challenged intrarectally with SIVmac239. Viral loads were measured in both peripheral and lymphoid compartments. Only the DNA prime-Ad5-boosted Mamu-A*01(+) cohort exhibited a notable reduction in peak plasma viral load (sevenfold) as well as in early set-point viral burdens in both plasma and lymphoid tissues (10-fold) relative to those observed in the control monkeys sharing the same Mamu-A*01 allele. The degree of control in each animal correlated with the levels of Gag-specific immunity before virus challenge. However, virus control was short-lived, and indications of viral escape were evident as early as 6 months postinfection. The implications of these results in vaccine design and clinical testing are discussed.

* Corresponding author. Mailing address: Department of Vaccines and Biologics Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486. Phone: (215) 652-3129. Fax: (215) 652-7320. E-mail: danilo_casimiro{at}merck.com.

Journal of Virology, December 2005, p. 15547-15555, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15547-15555.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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