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Interleukin-15 resp...
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Barrenäs, FredrikUppsala universitet,Beräkningsbiologi och bioinformatik
(författare)
Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy
- Artikel/kapitelEngelska2021
Förlag, utgivningsår, omfång ...
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2021-07-06
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Public Library of Science (PLoS),2021
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-451560
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-451560URI
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https://doi.org/10.1371/journal.ppat.1009278DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Hansen, Scott G.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Law, LynnUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Driscoll, ConnorUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Green, Richard R.Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Smith, EliseUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Chang, JeanUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Golez, InahUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Urion, TarynUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Peng, XinxiaNorth Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC USA.
(författare)
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Whitmore, LeanneUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Newhouse, DanielUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Hughes, Colette M.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Morrow, DavidOregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Randall, Kurt T.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Selseth, Andrea N.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Ford, Julia C.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Gilbride, Roxanne M.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Randall, Bryan E.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Ainslie, EmilyOregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Oswald, KelliNorth Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
(författare)
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Shoemaker, RebeccaNorth Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
(författare)
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Fast, RandyNorth Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
(författare)
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Bosche, William J.North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
(författare)
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Axthelm, Michael K.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Fukazawa, YoshinoriOregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Pavlakis, George N.Leidos Biomedical Res Inc, Frederick Natl Lab, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA.
(författare)
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Felber, Barbara K.Natl Canc Inst Frederick, Human Retrovirus Sect, Vaccine Branch, Frederick, MD USA.
(författare)
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Fourati, SlimNatl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA.
(författare)
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Sekaly, Rafick-PierreNatl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA.
(författare)
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Lifson, Jeffrey D.North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.
(författare)
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Komorowski, JanUppsala universitet,Beräkningsbiologi och bioinformatik(Swepub:uu)jakom133
(författare)
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Kosmider, EwelinaCase 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.
(författare)
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Shao, DanicaCase 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.
(författare)
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Song, WenjunCase 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.
(författare)
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Edlefsen, Paul T.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.
(författare)
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Picker, Louis J.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
(författare)
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Gale, Michael, Jr.Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
(författare)
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Uppsala universitetBeräkningsbiologi och bioinformatik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:PLoS Pathogens: Public Library of Science (PLoS)17:71553-73661553-7374
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Till lärosätets databas
- Av författaren/redakt...
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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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visa fler...
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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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