title: Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with dna and recombinant adenoviral vaccine vectors expressing Gag.
abstract: 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.
authors.affiliation: Department of Vaccines and Biologics Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486, USA. danilo_casimiro@merck.com
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Fubao
authors.initials: F
authors.lastname: Wang
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Tobery
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Davies
authors.forename: Adrian B
authors.initials: AB
authors.lastname: McDermott
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Arthur
authors.initials: A
authors.lastname: Fridman
authors.forename: Ansu
authors.initials: A
authors.lastname: Bagchi
authors.forename: Lynda G
authors.initials: LG
authors.lastname: Tussey
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bett
authors.forename: Adam C
authors.initials: AC
authors.lastname: Finnefrock
authors.forename: Tong-ming
authors.initials: TM
authors.lastname: Fu
authors.forename: Aimin
authors.initials: A
authors.lastname: Tang
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wilson
authors.forename: Minchun
authors.initials: M
authors.lastname: Chen
authors.forename: Helen C
authors.initials: HC
authors.lastname: Perry
authors.forename: Gwendolyn J
authors.initials: GJ
authors.lastname: Heidecker
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Freed
authors.forename: Anthony
authors.initials: A
authors.lastname: Carella
authors.forename: Kara S
authors.initials: KS
authors.lastname: Punt
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Sykes
authors.forename: Lingyi
authors.initials: L
authors.lastname: Huang
authors.forename: Virginia I
authors.initials: VI
authors.lastname: Ausensi
authors.forename: Margaret
authors.initials: M
authors.lastname: Bachinsky
authors.forename: Usha
authors.initials: U
authors.lastname: Sadasivan-Nair
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015683:Gene Products, gag / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors; D007114:Immunization; D008253:Macaca mulatta; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D015683:Gene Products, gag; D019444:Vaccines, DNA