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 SFVmac239 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 SFVmac239. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 15547-15555 |
| Number of pages | 9 |
| Journal | Journal of Virology |
| Volume | 79 |
| Issue number | 24 |
| DOIs | |
| State | Published - Dec 1 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with DNA and recombinant adenoviral vaccine vectors expressing Gag. / Casimiro, Danilo R.; Wang, Fubao; Schleif, William A.; Liang, Xiaoping; Zhang, Zhi Qiang; Tobery, Timothy W.; Davies, Mary Ellen; McDermott, Adrian B.; O'Connor, David H.; Fridman, Arthur; Bagchi, Ansu; Tussey, Lynda G.; Bett, Andrew J.; Finnefrock, Adam C.; Fu, Tong Ming; Tang, Aimin; Wilson, Keith A.; Chen, Minchun; Perry, Helen C.; Heidecker, Gwendolyn J.; Freed, Daniel C.; Carella, Anthony; Punt, Kara S.; Sykes, Kara J.; Huang, Lingyi; Ausensi, Virginia I.; Bachinsky, Margaret; Sadasivan-Nair, Usha; Watkins, David; Emini, Emilio A.; Shiver, John W.
In: Journal of Virology, Vol. 79, No. 24, 01.12.2005, p. 15547-15555.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with DNA and recombinant adenoviral vaccine vectors expressing Gag
AU - Casimiro, Danilo R.
AU - Wang, Fubao
AU - Schleif, William A.
AU - Liang, Xiaoping
AU - Zhang, Zhi Qiang
AU - Tobery, Timothy W.
AU - Davies, Mary Ellen
AU - McDermott, Adrian B.
AU - O'Connor, David H.
AU - Fridman, Arthur
AU - Bagchi, Ansu
AU - Tussey, Lynda G.
AU - Bett, Andrew J.
AU - Finnefrock, Adam C.
AU - Fu, Tong Ming
AU - Tang, Aimin
AU - Wilson, Keith A.
AU - Chen, Minchun
AU - Perry, Helen C.
AU - Heidecker, Gwendolyn J.
AU - Freed, Daniel C.
AU - Carella, Anthony
AU - Punt, Kara S.
AU - Sykes, Kara J.
AU - Huang, Lingyi
AU - Ausensi, Virginia I.
AU - Bachinsky, Margaret
AU - Sadasivan-Nair, Usha
AU - Watkins, David
AU - Emini, Emilio A.
AU - Shiver, John W.
PY - 2005/12/1
Y1 - 2005/12/1
N2 - 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 SFVmac239 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 SFVmac239. 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.
AB - 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 SFVmac239 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 SFVmac239. 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=29244455769&partnerID=8YFLogxK
U2 - 10.1128/JVI.79.24.15547-15555.2005
DO - 10.1128/JVI.79.24.15547-15555.2005
M3 - Article
C2 - 16306625
AN - SCOPUS:29244455769
VL - 79
SP - 15547
EP - 15555
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 24
ER -