Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239

Helen Horton, Thorsten U. Vogel, Donald K. Carter, Kathy Vielhuber, Deborah H. Fuller, Tim Shipley, James T. Fuller, Kevin J. Kunstman, Gerd Sutter, David C. Montefiori, Volker Erfle, Ronald C. Desrosiers, Nancy Wilson, Louis Picker, Steven M. Wolinsky, Chenxi Wang, David B. Allison, David I. Watkins

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Producing a prophylactic vaccine for human immunodeficiency virus (HIV) has proven to be a challenge. Most biological isolates of HIV are difficult to neutralize, so that conventional subunit-based antibody-inducing vaccines are unlikely to be very effective. In the rhesus macaque model, some protection was afforded by DNA/recombinant viral vector vaccines. However, these studies used as the challenge virus SHIV-89.6P, which is neutralizable, making it difficult to determine whether the observed protection was due to cellular immunity, humoral immunity, or a combination of both. In this study, we used a DNA prime/modified vaccinia virus Ankara boost regimen to immunize rhesus macaques against nearly all simian immunodeficiency virus (SIV) proteins. These animals were challenged intrarectally with pathogenic molecularly cloned SIVmac239, which is resistant to neutralization. The immunization regimen resulted in the induction of virus-specific CD8+ and CD4+ responses in all vaccinees. Although anamnestic neutralizing antibody responses against laboratory-adapted SIVmac251 developed after the challenge, no neutralizing antibodies against SIVmac239 were detectable. Vaccinated animals had significantly reduced peak viremia compared with controls (P <0.01). However, despite the induction of virus-specific cellular immune responses and reduced peak viral loads, most animals still suffered from gradual CD4 depletion and progressed to disease.

Original languageEnglish (US)
Pages (from-to)7187-7202
Number of pages16
JournalJournal of Virology
Volume76
Issue number14
DOIs
StatePublished - Jul 2002

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Vaccinia virus
virus replication
Macaca mulatta
disease course
Disease Progression
Virus Activation
Immunization
immunization
T-lymphocytes
Human immunodeficiency virus
Neutralizing Antibodies
T-Lymphocytes
neutralizing antibodies
Cellular Immunity
cell-mediated immunity
viruses
DNA
Vaccines

ASJC Scopus subject areas

  • Immunology

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Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239. / Horton, Helen; Vogel, Thorsten U.; Carter, Donald K.; Vielhuber, Kathy; Fuller, Deborah H.; Shipley, Tim; Fuller, James T.; Kunstman, Kevin J.; Sutter, Gerd; Montefiori, David C.; Erfle, Volker; Desrosiers, Ronald C.; Wilson, Nancy; Picker, Louis; Wolinsky, Steven M.; Wang, Chenxi; Allison, David B.; Watkins, David I.

In: Journal of Virology, Vol. 76, No. 14, 07.2002, p. 7187-7202.

Research output: Contribution to journalArticle

Horton, H, Vogel, TU, Carter, DK, Vielhuber, K, Fuller, DH, Shipley, T, Fuller, JT, Kunstman, KJ, Sutter, G, Montefiori, DC, Erfle, V, Desrosiers, RC, Wilson, N, Picker, L, Wolinsky, SM, Wang, C, Allison, DB & Watkins, DI 2002, 'Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239', Journal of Virology, vol. 76, no. 14, pp. 7187-7202. https://doi.org/10.1128/JVI.76.14.7187-7202.2002
Horton, Helen ; Vogel, Thorsten U. ; Carter, Donald K. ; Vielhuber, Kathy ; Fuller, Deborah H. ; Shipley, Tim ; Fuller, James T. ; Kunstman, Kevin J. ; Sutter, Gerd ; Montefiori, David C. ; Erfle, Volker ; Desrosiers, Ronald C. ; Wilson, Nancy ; Picker, Louis ; Wolinsky, Steven M. ; Wang, Chenxi ; Allison, David B. ; Watkins, David I. / Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression following challenge with pathogenic SIVmac239. In: Journal of Virology. 2002 ; Vol. 76, No. 14. pp. 7187-7202.
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abstract = "Producing a prophylactic vaccine for human immunodeficiency virus (HIV) has proven to be a challenge. Most biological isolates of HIV are difficult to neutralize, so that conventional subunit-based antibody-inducing vaccines are unlikely to be very effective. In the rhesus macaque model, some protection was afforded by DNA/recombinant viral vector vaccines. However, these studies used as the challenge virus SHIV-89.6P, which is neutralizable, making it difficult to determine whether the observed protection was due to cellular immunity, humoral immunity, or a combination of both. In this study, we used a DNA prime/modified vaccinia virus Ankara boost regimen to immunize rhesus macaques against nearly all simian immunodeficiency virus (SIV) proteins. These animals were challenged intrarectally with pathogenic molecularly cloned SIVmac239, which is resistant to neutralization. The immunization regimen resulted in the induction of virus-specific CD8+ and CD4+ responses in all vaccinees. Although anamnestic neutralizing antibody responses against laboratory-adapted SIVmac251 developed after the challenge, no neutralizing antibodies against SIVmac239 were detectable. Vaccinated animals had significantly reduced peak viremia compared with controls (P <0.01). However, despite the induction of virus-specific cellular immune responses and reduced peak viral loads, most animals still suffered from gradual CD4 depletion and progressed to disease.",
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AU - Horton, Helen

AU - Vogel, Thorsten U.

AU - Carter, Donald K.

AU - Vielhuber, Kathy

AU - Fuller, Deborah H.

AU - Shipley, Tim

AU - Fuller, James T.

AU - Kunstman, Kevin J.

AU - Sutter, Gerd

AU - Montefiori, David C.

AU - Erfle, Volker

AU - Desrosiers, Ronald C.

AU - Wilson, Nancy

AU - Picker, Louis

AU - Wolinsky, Steven M.

AU - Wang, Chenxi

AU - Allison, David B.

AU - Watkins, David I.

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