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Sökning: WFRF:(Law Lynn) > (2021) > Interleukin-15 resp...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00009241naa a2200769 4500
001oai:DiVA.org:uu-451560
003SwePub
008210909s2021 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4515602 URI
0247 a https://doi.org/10.1371/journal.ppat.10092782 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Barrenäs, Fredriku Uppsala universitet,Beräkningsbiologi och bioinformatik4 aut0 (Swepub:uu)carba111
2451 0a Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy
264 c 2021-07-06
264 1b Public Library of Science (PLoS),c 2021
338 a electronic2 rdacarrier
520 a 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.
650 7a NATURVETENSKAPx Biologix Immunologi0 (SwePub)106052 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Immunology0 (SwePub)106052 hsv//eng
7001 a Hansen, Scott G.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Law, Lynnu Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Driscoll, Connoru Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Green, Richard R.u Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Smith, Eliseu Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Chang, Jeanu Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Golez, Inahu Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Urion, Tarynu Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Peng, Xinxiau North Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC USA.4 aut
7001 a Whitmore, Leanneu Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Newhouse, Danielu Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7001 a Hughes, Colette M.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Morrow, Davidu Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Randall, Kurt T.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Selseth, Andrea N.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Ford, Julia C.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Gilbride, Roxanne M.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Randall, Bryan E.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Ainslie, Emilyu Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Oswald, Kelliu North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.4 aut
7001 a Shoemaker, Rebeccau North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.4 aut
7001 a Fast, Randyu North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.4 aut
7001 a Bosche, William J.u North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.4 aut
7001 a Axthelm, Michael K.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Fukazawa, Yoshinoriu Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Pavlakis, George N.u Leidos Biomedical Res Inc, Frederick Natl Lab, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA.4 aut
7001 a Felber, Barbara K.u Natl Canc Inst Frederick, Human Retrovirus Sect, Vaccine Branch, Frederick, MD USA.4 aut
7001 a Fourati, Slimu Natl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA.4 aut
7001 a Sekaly, Rafick-Pierreu Natl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA.4 aut
7001 a Lifson, Jeffrey D.u North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA.4 aut
7001 a Komorowski, Janu Uppsala universitet,Beräkningsbiologi och bioinformatik4 aut0 (Swepub:uu)jakom133
7001 a Kosmider, Ewelinau 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.4 aut
7001 a Shao, Danicau 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.4 aut
7001 a Song, Wenjunu 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.4 aut
7001 a Edlefsen, Paul T.u 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.4 aut
7001 a Picker, Louis J.u Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.;Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.4 aut
7001 a Gale, Michael, Jr.u Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.4 aut
7102 a Uppsala universitetb Beräkningsbiologi och bioinformatik4 org
7730 t PLoS Pathogensd : Public Library of Science (PLoS)g 17:7q 17:7x 1553-7366x 1553-7374
8564 u https://doi.org/10.1371/journal.ppat.1009278y Fulltext
8564 u https://uu.diva-portal.org/smash/get/diva2:1592748/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 u https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009278&type=printable
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-451560
8564 8u https://doi.org/10.1371/journal.ppat.1009278

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