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Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy

  1. Author:
    Verweij, Marieke C.
    Hansen, Scott G.
    Iyer, Ravi
    John, Nessy
    Malouli, Daniel
    Morrow, David
    Scholz, Isabel
    Womack, Jennie
    Abdulhaqq, Shaheed
    Gilbride, Roxanne M.
    Hughes, Colette M.
    Ventura, Abigail B.
    Ford, Julia C.
    Selseth, Andrea N.
    Oswald,Kelli
    Shoemaker,Rebecca
    Berkemeier,Brian
    Bosche,Bj
    Hull,Mike
    Shao, Jason
    Sacha, Jonah B.
    Axthelm, Michael K.
    Edlefsen, Paul T.
    Lifson,Jeffrey
    Picker, Louis J.
    Frueh, Klaus

  2. Author Address

    Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA.Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.Frederick Natl Lab, AIDS & Canc Virus Program, Frederick, MD 21702 USA.Fred Hutchinson Canc Res Ctr, Populat Sci Program, Seattle, WA 98109 USA.Fred Hutchinson Canc Res Ctr, Computat Biol Program, Seattle, WA 98109 USA.
    1. Year: 2021
    2. Date: Apr 30
    3. Epub Date: 2021 03 25
  2. Journal: Science
  3. Amer Assoc Advancement Science
    1. 372
    2. 6451
  5. Type of Article: Article
  6. Article Number: ARTN eabe9233
  7. ISSN: 0036-8075
  1. Abstract:

    Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8(+) T cells recognizing epitopes presented by major histocompatibility complex II (MHC-II) and MHC-E but not MHC-Ia. These immune responses mediate replication arrest of SIV in 50 to 60% of monkeys. We show that the peptide VMAPRTLLL (VL9) embedded within the RhCMV protein Rh67 promotes intracellular MHC-E transport and recognition of RhCMV-infected fibroblasts by MHC-E-restricted CD8(+) T cells. Deletion or mutation of viral VL9 abrogated MHC-E-restricted CD8(+) T cell priming, resulting in CD8(+) T cell responses exclusively targeting MHC-II-restricted epitopes. These responses were comparable in magnitude and differentiation to responses elicited by 68-1 vectors but did not protect against SIV. Thus, Rh67-enabled direct priming of MHC-E-restricted T cells is crucial for RhCMV/SIV vaccine efficacy.

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External Sources

  1. View Full Text
  2. DOI: 10.1126/science.abe9233
  3. PMID: 33766941
  4. PMCID: PMC8354429
  5. View record in Web of Science®
  6. WOS: 000645554100038

Library Notes

  1. Fiscal Year: FY2020-2021
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