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 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 Citations (Scopus)

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

Fingerprint

Simian Immunodeficiency Virus
Virus Diseases
Virus Replication
Disease Progression
Macaca mulatta
Vaccines
AIDS Vaccines
T-Lymphocytes
Viral Load
Primate Lentiviruses
Vaccinia
Viremia
Immune System
Mucous Membrane
Acquired Immunodeficiency Syndrome
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression. / Engram, Jessica C.; Dunham, Richard M.; Makedonas, George; Vanderford, Thomas H.; Sumpter, Beth; Klatt, Nichole; Ratcliffe, Sarah J.; Garg, Seema; Paiardini, Mirko; McQuoid, Monica; Altman, John D.; Staprans, Silvija I.; Betts, Michael R.; Garber, David A.; Feinberg, Mark B.; Silvestri, Guido.

In: Journal of Immunology, Vol. 183, No. 1, 01.07.2009, p. 706-717.

Research output: Contribution to journalArticle

Engram, JC, Dunham, RM, Makedonas, G, Vanderford, TH, Sumpter, B, Klatt, N, Ratcliffe, SJ, Garg, S, Paiardini, M, McQuoid, M, Altman, JD, Staprans, SI, Betts, MR, Garber, DA, Feinberg, MB & 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, vol. 183, no. 1, pp. 706-717. https://doi.org/10.4049/jimmunol.0803746
Engram, Jessica C. ; Dunham, Richard M. ; Makedonas, George ; Vanderford, Thomas H. ; Sumpter, Beth ; Klatt, Nichole ; Ratcliffe, Sarah J. ; Garg, Seema ; Paiardini, Mirko ; McQuoid, Monica ; Altman, John D. ; Staprans, Silvija I. ; Betts, Michael R. ; Garber, David A. ; Feinberg, Mark B. ; Silvestri, Guido. / Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression. In: Journal of Immunology. 2009 ; Vol. 183, No. 1. pp. 706-717.
@article{2124420df3b74d78b200ccb60238967e,
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 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.",
author = "Engram, {Jessica C.} and Dunham, {Richard M.} and George Makedonas and Vanderford, {Thomas H.} and Beth Sumpter and Nichole Klatt and Ratcliffe, {Sarah J.} and Seema Garg and Mirko Paiardini and Monica McQuoid and Altman, {John D.} and Staprans, {Silvija I.} and Betts, {Michael R.} and Garber, {David A.} and Feinberg, {Mark B.} and Guido Silvestri",
year = "2009",
month = "7",
day = "1",
doi = "10.4049/jimmunol.0803746",
language = "English (US)",
volume = "183",
pages = "706--717",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression

AU - Engram, Jessica C.

AU - Dunham, Richard M.

AU - Makedonas, George

AU - Vanderford, Thomas H.

AU - Sumpter, Beth

AU - Klatt, Nichole

AU - Ratcliffe, Sarah J.

AU - Garg, Seema

AU - Paiardini, Mirko

AU - McQuoid, Monica

AU - Altman, John D.

AU - Staprans, Silvija I.

AU - Betts, Michael R.

AU - Garber, David A.

AU - Feinberg, Mark B.

AU - Silvestri, Guido

PY - 2009/7/1

Y1 - 2009/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=68949110126&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68949110126&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0803746

DO - 10.4049/jimmunol.0803746

M3 - Article

C2 - 19542473

AN - SCOPUS:68949110126

VL - 183

SP - 706

EP - 717

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -