title: Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression.
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 MVADeltaudg 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 approximately 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, SIV-specific 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.
authors: Department of Pathology, University of Pennsylvania, Philadelphia, 19104, USA.
authors: Jessica C
authors: JC
authors: Engram
authors: Richard M
authors: RM
authors: Dunham
authors: George
authors: G
authors: Makedonas
authors: Thomas H
authors: TH
authors: Vanderford
authors: Beth
authors: B
authors: Sumpter
authors: Nichole R
authors: NR
authors: Klatt
authors: Sarah J
authors: SJ
authors: Ratcliffe
authors: Seema
authors: S
authors: Garg
authors: Mirko
authors: M
authors: Paiardini
authors: Monica
authors: M
authors: McQuoid
authors: John D
authors: JD
authors: Altman
authors: Silvija I
authors: SI
authors: Staprans
authors: Michael R
authors: MR
authors: Betts
authors: David A
authors: DA
authors: Garber
authors: Mark B
authors: MB
authors: Feinberg
authors: Guido
authors: G
authors: Silvestri
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D018449:SAIDS Vaccines