Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with dna and recombinant adenoviral vaccine vectors expressing Gag.
Journal of virology 2005 Dec 1; 79(24):15547-55
Casimiro D DR, Wang F F, Schleif W WA, Liang X X, Zhang Z ZQ, Tobery T TW, Davies M ME, McDermott A AB, O'Connor D DH, Fridman A A, Bagchi A A, Tussey L LG, Bett A AJ, Finnefrock A AC, Fu T TM, Tang A A, Wilson K KA, Chen M M, Perry H HC, Heidecker G GJ, Freed D DC, Carella A A, Punt K KS, Sykes K KJ, Huang L L, Ausensi V VI, Bachinsky M M, Sadasivan-Nair U U, Watkins D DI, Emini E EA, Shiver J JW
Department of Vaccines and Biologics Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486, USA. danilo_casimiro@merck.com
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.