The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles
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...
| Published in: | Blood Advances |
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952920311149 |
| _version_ | 1849991144236122112 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Gabriela M. Webb |
| collection | DOAJ |
| container_title | Blood Advances |
| description | 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. |
| format | Article |
| id | doaj-art-eefee46bd3354844aa52e77eb0fb72eb |
| institution | Directory of Open Access Journals |
| issn | 2473-9529 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| spelling | doaj-art-eefee46bd3354844aa52e77eb0fb72eb2025-08-20T00:53:32ZengElsevierBlood Advances2473-95292018-01-0122768410.1182/bloodadvances.2017012971The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell folliclesGabriela M. Webb0Shengbin Li1Gwantwa Mwakalundwa2Joy M. Folkvord3Justin M. Greene4Jason S. Reed5Jeffery J. Stanton6Alfred W. Legasse7Theodore Hobbs8Lauren D. Martin9Byung S. Park10James B. Whitney11Emily K. Jeng12Hing C. Wong13Douglas F. Nixon14R. Brad Jones15Elizabeth Connick16Pamela J. Skinner17Jonah B. Sacha18Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR;; Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;Division of Infectious Diseases, University of Arizona, Tucson, AZ;Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR;; Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR;; Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR;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;Altor BioScience Corporation, Miramar, FL;Altor BioScience Corporation, Miramar, FL;Department of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DCDepartment of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DCDivision of Infectious Diseases, University of Arizona, Tucson, AZ;Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN;; Pamela J. Skinner, University of Minnesota, 1971 Commonwealth Ave, St. Paul, MN;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 97006Abstract: 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.http://www.sciencedirect.com/science/article/pii/S2473952920311149 |
| spellingShingle | 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 The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles |
| title | The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles |
| title_full | The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles |
| title_fullStr | The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles |
| title_full_unstemmed | The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles |
| title_short | The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles |
| title_sort | human il 15 superagonist alt 803 directs siv specific cd8 t cells into b cell follicles |
| url | http://www.sciencedirect.com/science/article/pii/S2473952920311149 |
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