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

  • Barrenäs, FredrikUppsala universitet,Beräkningsbiologi och bioinformatik (författare)

Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-07-06
  • Public Library of Science (PLoS),2021
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-451560
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-451560URI
  • https://doi.org/10.1371/journal.ppat.1009278DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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 ...)

  • 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)
  • Law, LynnUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Driscoll, ConnorUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Green, Richard R.Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Smith, EliseUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Chang, JeanUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Golez, InahUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Urion, TarynUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Peng, XinxiaNorth Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC USA. (författare)
  • Whitmore, LeanneUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Newhouse, DanielUniv Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Oswald, KelliNorth Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA. (författare)
  • Shoemaker, RebeccaNorth Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA. (författare)
  • Fast, RandyNorth Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA. (författare)
  • Bosche, William J.North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA. (författare)
  • 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)
  • Fukazawa, YoshinoriOregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. (författare)
  • Pavlakis, George N.Leidos Biomedical Res Inc, Frederick Natl Lab, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA. (författare)
  • Felber, Barbara K.Natl Canc Inst Frederick, Human Retrovirus Sect, Vaccine Branch, Frederick, MD USA. (författare)
  • Fourati, SlimNatl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA. (författare)
  • Sekaly, Rafick-PierreNatl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA. (författare)
  • Lifson, Jeffrey D.North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA. (författare)
  • Komorowski, JanUppsala universitet,Beräkningsbiologi och bioinformatik(Swepub:uu)jakom133 (författare)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Gale, Michael, Jr.Univ Washington, Dept Immunol, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA. (författare)
  • Uppsala universitetBeräkningsbiologi och bioinformatik (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:PLoS Pathogens: Public Library of Science (PLoS)17:71553-73661553-7374

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