Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge

Nancy A. Wilson, Brandon F. Keele, Jason S. Reed, Shari M. Piaskowski, Caitlin E. MacNair, Andrew J. Bett, Xiaoping Liang, Fubao Wang, Elizabeth Thoryk, Gwendolyn J. Heidecker, Michael P. Citron, Lingyi Huang, Jing Lin, Salvatore Vitelli, Chanook D. Ahn, Masahiko Kaizu, Nicholas J. Maness, Matthew R. Reynolds, Thomas C. Friedrich, John T. Loffredo & 10 others Eva G. Rakasz, Stephen Erickson, David B. Allison, Michael Piatak, Jeffrey D. Lifson, John W. Shiver, Danilo R. Casimiro, George M. Shaw, Beatrice H. Hahn, David Watkins

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

All human immunodeficiency virus (HIV) vaccine efficacy trials to date have ended in failure. Structural features of the Env glycoprotein and its enormous variability have frustrated efforts to induce broadly reactive neutralizing antibodies. To explore the extent to which vaccine-induced cellular immune responses, in the absence of neutralizing antibodies, can control replication of a heterologous, mucosal viral challenge, we vaccinated eight macaques with a DNA/Ad5 regimen expressing all of the proteins of SIVmac239 except Env. Vaccinees mounted high-frequency T-cell responses against 11 to 34 epitopes. We challenged the vaccinees and eight naïve animals with the heterologous biological isolate SIVsmE660, using a regimen intended to mimic typical HIV exposures resulting in infection. Viral loads in the vaccinees were significantly less at both the peak (1.9-log reduction; P < 0.03) and at the set point (2.6-log reduction; P < 0.006) than those in control naïve animals. Five of eight vaccinated macaques controlled acute peak viral replication to less than 80,000 viral RNA (vRNA) copy eq/ml and to less than 100 vRNA copy eq/ml in the chronic phase. Our results demonstrate that broad vaccine-induced cellular immune responses can effectively control replication of a pathogenic, heterologous AIDS virus, suggesting that T-cell-based vaccines may have greater potential than previously appreciated.

Original languageEnglish
Pages (from-to)6508-6521
Number of pages14
JournalJournal of Virology
Volume83
Issue number13
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Virus Replication
virus replication
Vaccines
vaccines
Human immunodeficiency virus
Viral RNA
HIV
Macaca
Neutralizing Antibodies
neutralizing antibodies
Cellular Immunity
cell-mediated immunity
T-lymphocytes
RNA
env Gene Products
T-Lymphocytes
viral load
Viral Load

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge. / Wilson, Nancy A.; Keele, Brandon F.; Reed, Jason S.; Piaskowski, Shari M.; MacNair, Caitlin E.; Bett, Andrew J.; Liang, Xiaoping; Wang, Fubao; Thoryk, Elizabeth; Heidecker, Gwendolyn J.; Citron, Michael P.; Huang, Lingyi; Lin, Jing; Vitelli, Salvatore; Ahn, Chanook D.; Kaizu, Masahiko; Maness, Nicholas J.; Reynolds, Matthew R.; Friedrich, Thomas C.; Loffredo, John T.; Rakasz, Eva G.; Erickson, Stephen; Allison, David B.; Piatak, Michael; Lifson, Jeffrey D.; Shiver, John W.; Casimiro, Danilo R.; Shaw, George M.; Hahn, Beatrice H.; Watkins, David.

In: Journal of Virology, Vol. 83, No. 13, 01.07.2009, p. 6508-6521.

Research output: Contribution to journalArticle

Wilson, NA, Keele, BF, Reed, JS, Piaskowski, SM, MacNair, CE, Bett, AJ, Liang, X, Wang, F, Thoryk, E, Heidecker, GJ, Citron, MP, Huang, L, Lin, J, Vitelli, S, Ahn, CD, Kaizu, M, Maness, NJ, Reynolds, MR, Friedrich, TC, Loffredo, JT, Rakasz, EG, Erickson, S, Allison, DB, Piatak, M, Lifson, JD, Shiver, JW, Casimiro, DR, Shaw, GM, Hahn, BH & Watkins, D 2009, 'Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge', Journal of Virology, vol. 83, no. 13, pp. 6508-6521. https://doi.org/10.1128/JVI.00272-09
Wilson, Nancy A. ; Keele, Brandon F. ; Reed, Jason S. ; Piaskowski, Shari M. ; MacNair, Caitlin E. ; Bett, Andrew J. ; Liang, Xiaoping ; Wang, Fubao ; Thoryk, Elizabeth ; Heidecker, Gwendolyn J. ; Citron, Michael P. ; Huang, Lingyi ; Lin, Jing ; Vitelli, Salvatore ; Ahn, Chanook D. ; Kaizu, Masahiko ; Maness, Nicholas J. ; Reynolds, Matthew R. ; Friedrich, Thomas C. ; Loffredo, John T. ; Rakasz, Eva G. ; Erickson, Stephen ; Allison, David B. ; Piatak, Michael ; Lifson, Jeffrey D. ; Shiver, John W. ; Casimiro, Danilo R. ; Shaw, George M. ; Hahn, Beatrice H. ; Watkins, David. / Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge. In: Journal of Virology. 2009 ; Vol. 83, No. 13. pp. 6508-6521.
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AU - Liang, Xiaoping

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AU - Allison, David B.

AU - Piatak, Michael

AU - Lifson, Jeffrey D.

AU - Shiver, John W.

AU - Casimiro, Danilo R.

AU - Shaw, George M.

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