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Interleukin-15 resp...
Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy
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- Barrenäs, Fredrik (author)
- Uppsala universitet,Beräkningsbiologi och bioinformatik
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- Hansen, Scott G. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Law, Lynn (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Driscoll, Connor (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Green, Richard R. (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Smith, Elise (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Chang, Jean (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Golez, Inah (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Urion, Taryn (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Peng, Xinxia (author)
- North Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC USA.
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- Whitmore, Leanne (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Newhouse, Daniel (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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- Hughes, Colette M. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Morrow, David (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Randall, Kurt T. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Selseth, Andrea N. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Ford, Julia C. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Gilbride, Roxanne M. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Randall, Bryan E. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Ainslie, Emily (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Oswald, Kelli (author)
- North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
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- Shoemaker, Rebecca (author)
- North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
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- Fast, Randy (author)
- North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
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- Bosche, William J. (author)
- North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
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- Axthelm, Michael K. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Fukazawa, Yoshinori (author)
- Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Pavlakis, George N. (author)
- Leidos Biomedical Res Inc, Frederick Natl Lab, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA.
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- Felber, Barbara K. (author)
- Natl Canc Inst Frederick, Human Retrovirus Sect, Vaccine Branch, Frederick, MD USA.
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- Fourati, Slim (author)
- Natl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA.
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- Sekaly, Rafick-Pierre (author)
- Natl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA.
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- Lifson, Jeffrey D. (author)
- North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
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- Komorowski, Jan (author)
- Uppsala universitet,Beräkningsbiologi och bioinformatik
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- Kosmider, Ewelina (author)
- Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.;Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA.
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- Shao, Danica (author)
- Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.;Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA.
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- Song, Wenjun (author)
- Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.;Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA.
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- Edlefsen, Paul T. (author)
- Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.;Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA.
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- Picker, Louis J. (author)
- Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
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- Gale, Michael, Jr. (author)
- Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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(creator_code:org_t)
- 2021-07-06
- 2021
- English.
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:7
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Abstract
Subject headings
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- Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68-1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in similar to 55% of vaccinated RMs with no protection in the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8(+) T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in 68-1 RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that 68-1 RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including immune cell, toll-like receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly correlating with subsequent vaccine efficacy. Treatment of a separate RM cohort with IL-15 confirmed the central involvement of this cytokine in the protection signature, linking the major innate and adaptive immune gene expression networks that correlate with RhCMV/SIV vaccine efficacy. This change-from-baseline IL-15 response signature was also demonstrated to significantly correlate with vaccine efficacy in an independent validation cohort of vaccinated and challenged RMs. The differential IL-15 gene set response to vaccination strongly correlated with the pre-vaccination activity of this pathway, with reduced baseline expression of IL-15 response genes significantly correlating with higher vaccine-induced induction of IL-15 signaling and subsequent vaccine protection, suggesting that a robust de novo vaccine-induced IL-15 signaling response is needed to program vaccine efficacy. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8(+) T cell function, that support the ability of vaccine-elicited unconventionally restricted CD8(+) T cells to mediate protection against SIV challenge.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Barrenäs, Fredri ...
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Hansen, Scott G.
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Law, Lynn
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Driscoll, Connor
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Green, Richard R ...
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Smith, Elise
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show more...
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Chang, Jean
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Golez, Inah
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Urion, Taryn
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Peng, Xinxia
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Whitmore, Leanne
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Newhouse, Daniel
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Hughes, Colette ...
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Morrow, David
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Randall, Kurt T.
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Selseth, Andrea ...
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Ford, Julia C.
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Gilbride, Roxann ...
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Randall, Bryan E ...
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Ainslie, Emily
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Oswald, Kelli
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Shoemaker, Rebec ...
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Fast, Randy
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Bosche, William ...
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Axthelm, Michael ...
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Fukazawa, Yoshin ...
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Pavlakis, George ...
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Felber, Barbara ...
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Fourati, Slim
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Sekaly, Rafick-P ...
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Lifson, Jeffrey ...
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Komorowski, Jan
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Kosmider, Ewelin ...
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Shao, Danica
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Song, Wenjun
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Edlefsen, Paul T ...
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Picker, Louis J.
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Gale, Michael, J ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
- Articles in the publication
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PLoS Pathogens
- By the university
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Uppsala University