Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine

Scott Hansen, Julia C. Ford, Matthew S. Lewis, Abigail B. Ventura, Colette M. Hughes, Lia Coyne-Johnson, Nathan Whizin, Kelli Oswald, Rebecca Shoemaker, Tonya Swanson, Alfred W. Legasse, Maria J. Chiuchiolo, Christopher L. Parks, Michael Axthelm, Jay Nelson, Michael A. Jarvis, Michael Piatak, Jeffrey D. Lifson, Louis Picker

Research output: Contribution to journalArticle

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Abstract

The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms1-3. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control4. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors5 establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (TEM) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIVMAC239 infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (≥1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4+ memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8+ T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8+ or CD4+ lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated TEM responses might significantly contribute to an efficacious HIV/AIDS vaccine.

Original languageEnglish (US)
Pages (from-to)523-527
Number of pages5
JournalNature
Volume473
Issue number7348
DOIs
StatePublished - May 26 2011

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Simian Immunodeficiency Virus
Vaccines
T-Lymphocytes
Cytomegalovirus
Macaca mulatta
Satellite Viruses
Adenoviridae
vif Gene Products
Acquired Immunodeficiency Syndrome
HIV
Lymphocyte Depletion
Lentivirus
Viremia
Virus Diseases
Virus Replication
Infection
Viral Load
Limit of Detection
Immunity
Lymph Nodes

ASJC Scopus subject areas

  • General

Cite this

Hansen, S., Ford, J. C., Lewis, M. S., Ventura, A. B., Hughes, C. M., Coyne-Johnson, L., ... Picker, L. (2011). Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature, 473(7348), 523-527. https://doi.org/10.1038/nature10003

Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. / Hansen, Scott; Ford, Julia C.; Lewis, Matthew S.; Ventura, Abigail B.; Hughes, Colette M.; Coyne-Johnson, Lia; Whizin, Nathan; Oswald, Kelli; Shoemaker, Rebecca; Swanson, Tonya; Legasse, Alfred W.; Chiuchiolo, Maria J.; Parks, Christopher L.; Axthelm, Michael; Nelson, Jay; Jarvis, Michael A.; Piatak, Michael; Lifson, Jeffrey D.; Picker, Louis.

In: Nature, Vol. 473, No. 7348, 26.05.2011, p. 523-527.

Research output: Contribution to journalArticle

Hansen, S, Ford, JC, Lewis, MS, Ventura, AB, Hughes, CM, Coyne-Johnson, L, Whizin, N, Oswald, K, Shoemaker, R, Swanson, T, Legasse, AW, Chiuchiolo, MJ, Parks, CL, Axthelm, M, Nelson, J, Jarvis, MA, Piatak, M, Lifson, JD & Picker, L 2011, 'Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine', Nature, vol. 473, no. 7348, pp. 523-527. https://doi.org/10.1038/nature10003
Hansen S, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011 May 26;473(7348):523-527. https://doi.org/10.1038/nature10003
Hansen, Scott ; Ford, Julia C. ; Lewis, Matthew S. ; Ventura, Abigail B. ; Hughes, Colette M. ; Coyne-Johnson, Lia ; Whizin, Nathan ; Oswald, Kelli ; Shoemaker, Rebecca ; Swanson, Tonya ; Legasse, Alfred W. ; Chiuchiolo, Maria J. ; Parks, Christopher L. ; Axthelm, Michael ; Nelson, Jay ; Jarvis, Michael A. ; Piatak, Michael ; Lifson, Jeffrey D. ; Picker, Louis. / Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. In: Nature. 2011 ; Vol. 473, No. 7348. pp. 523-527.
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