Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression

Jessica C. Engram, Richard M. Dunham, George Makedonas, Thomas H. Vanderford, Beth Sumpter, Nichole R. Klatt, Sarah J. Ratcliffe, Seema Garg, Mirko Paiardini, Monica McQuoid, John D. Altman, Silvija I. Staprans, Michael R. Betts, David A. Garber, Mark B. Feinberg, Guido Silvestri

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Our limited understanding of the interaction between primate lentiviruses and the host immune system complicates the design of an effective HIV/AIDS vaccine. To identify immunological correlates of protection from SIV disease progression, we immunized two groups of five rhesus macaques (RMs) with either modified vaccinia Ankara (MVA) or MVAΔudg vectors that expressed SIVmac239 Gag and Tat. Both vectors raised a SIV-specific CD8+ T cell response, with a magnitude that was greater in mucosal tissues than in peripheral blood. After challenge with SIVmac239, all vaccinated RMs showed mucosal and systemic CD8+ T cell recall responses that appeared faster and were of greater magnitude than those in five unvaccinated control animals. All vaccinated RMs showed a ∼1-log lower peak and early set-point SIV viral load than the unvaccinated animals, and then, by 8 wk postchallenge, exhibited levels of viremia similar to the controls. We observed a significant direct correlation between the magnitude of postchallenge SIV-specific CD8 + T cell responses and SIV viral load. However, vaccinated RMs showed no protection from either systemic or mucosal CD4+ T cell depletion and no improved survival. The observation that vaccine-induced, SIVspecific CD8+ T cells that partially control SIVmac239 virus replication fail to protect from immunological or clinical progression of SIV infection underscores both the complexity of AIDS pathogenesis and the challenges of properly assessing the efficacy of candidate AIDS vaccines.

Original languageEnglish (US)
Pages (from-to)706-717
Number of pages12
JournalJournal of Immunology
Volume183
Issue number1
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Engram, J. C., Dunham, R. M., Makedonas, G., Vanderford, T. H., Sumpter, B., Klatt, N. R., Ratcliffe, S. J., Garg, S., Paiardini, M., McQuoid, M., Altman, J. D., Staprans, S. I., Betts, M. R., Garber, D. A., Feinberg, M. B., & Silvestri, G. (2009). Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression. Journal of Immunology, 183(1), 706-717. https://doi.org/10.4049/jimmunol.0803746