The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles

Gabriela M. Webb; Shengbin Li; Gwantwa Mwakalundwa; Joy M. Folkvord; Justin M. Greene; Jason S. Reed; Jeffery J. Stanton; Alfred W. Legasse; Theodore Hobbs; Lauren D. Martin; Byung S. Park; James B. Whitney; Emily K. Jeng; Hing C. Wong; Douglas F. Nixon; R. Brad Jones; Elizabeth Connick; Pamela J. Skinner; Jonah B. Sacha

Blood Advances (Jan 2018)

The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles

Gabriela M. Webb,
Shengbin Li,
Gwantwa Mwakalundwa,
Joy M. Folkvord,
Justin M. Greene,
Jason S. Reed,
Jeffery J. Stanton,
Alfred W. Legasse,
Theodore Hobbs,
Lauren D. Martin,
Byung S. Park,
James B. Whitney,
Emily K. Jeng,
Hing C. Wong,
Douglas F. Nixon,
R. Brad Jones,
Elizabeth Connick,
Pamela J. Skinner,
Jonah B. Sacha

Affiliations

Gabriela M. Webb: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR;; Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;
Shengbin Li: Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;
Gwantwa Mwakalundwa: Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;
Joy M. Folkvord: Division of Infectious Diseases, University of Arizona, Tucson, AZ;
Justin M. Greene: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR;; Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;
Jason S. Reed: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR;; Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;
Jeffery J. Stanton: Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;
Alfred W. Legasse: Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;
Theodore Hobbs: Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;
Lauren D. Martin: Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;
Byung S. Park: Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;
James B. Whitney: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA;
Emily K. Jeng: Altor BioScience Corporation, Miramar, FL;
Hing C. Wong: Altor BioScience Corporation, Miramar, FL;
Douglas F. Nixon: Department of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC
R. Brad Jones: Department of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC
Elizabeth Connick: Division of Infectious Diseases, University of Arizona, Tucson, AZ;
Pamela J. Skinner: Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;; Pamela J. Skinner, University of Minnesota, 1971 Commonwealth Ave, St. Paul, MN;
Jonah B. Sacha: Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR;; Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;; Jonah B. Sacha, Oregon Health & Science University, 505 SW 185th Ave, Beaverton, OR 97006

Journal volume & issue: Vol. 2, no. 2
pp. 76 – 84

Abstract

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Abstract: Sequestering of latent HIV in follicular helper T cells within B-cell follicles that largely exclude cytotoxic T cells is a major barrier to cellular immune-based approaches to eradicate HIV. Here, we show that the clinical-grade human interleukin-15 (IL-15) superagonist ALT-803 activates and redirects simian immunodeficiency virus (SIV)–specific CD8+ T cells from the peripheral blood into B-cell follicles. In agreement with the increased trafficking of SIV-specific cytotoxic T cells to sites of cryptic viral replication, lymph nodes of elite controlling macaques contained fewer cells expressing SIV RNA or harboring SIV DNA post–ALT-803 treatment. These data establish ALT-803 as an immunotherapeutic for HIV and other chronic viral pathogens that evade host immunity by persisting in B-cell follicles.

Published in Blood Advances

ISSN: 2473-9529 (Print); 2473-9537 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine
Website: https://ashpublications.org/bloodadvances

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