Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with dna and recombinant adenoviral vaccine vectors expressing Gag.
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.
Casimiro
Danilo R
DR
Department of Vaccines and Biologics Research, Merck Research Laboratories, Merck & Co., West Point, Pennsylvania 19486, USA. danilo_casimiro@merck.com
Wang
Fubao
F
Schleif
William A
WA
Liang
Xiaoping
X
Zhang
Zhi-Qiang
ZQ
Tobery
Timothy W
TW
Davies
Mary-Ellen
ME
McDermott
Adrian B
AB
O'Connor
David H
DH
Fridman
Arthur
A
Bagchi
Ansu
A
Tussey
Lynda G
LG
Bett
Andrew J
AJ
Finnefrock
Adam C
AC
Fu
Tong-ming
TM
Tang
Aimin
A
Wilson
Keith A
KA
Chen
Minchun
M
Perry
Helen C
HC
Heidecker
Gwendolyn J
GJ
Freed
Daniel C
DC
Carella
Anthony
A
Punt
Kara S
KS
Sykes
Kara J
KJ
Huang
Lingyi
L
Ausensi
Virginia I
VI
Bachinsky
Margaret
M
Sadasivan-Nair
Usha
U
Watkins
David I
DI
Emini
Emilio A
EA
Shiver
John W
JW
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
D000914:Antibodies, Viral; D015683:Gene Products, gag; D019444:Vaccines, DNA