@article{5e63619791e3402b82c2294ede839d9a,
title = "Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy",
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.",
author = "Verweij, {Marieke C.} and Hansen, {Scott G.} and Ravi Iyer and Nessy John and Daniel Malouli and David Morrow and Isabel Scholz and Jennie Womack and Shaheed Abdulhaqq and Gilbride, {Roxanne M.} and Hughes, {Colette M.} and Ventura, {Abigail B.} and Ford, {Julia C.} and Selseth, {Andrea N.} and Kelli Oswald and Rebecca Shoemaker and Brian Berkemeier and Bosche, {William J.} and Michael Hull and Jason Shao and Sacha, {Jonah B.} and Axthelm, {Michael K.} and Edlefsen, {Paul T.} and Lifson, {Jeffrey D.} and Picker, {Louis J.} and Klaus Fr{\"u}h",
note = "Funding Information: We thank T. Whitmer, A. Bhusari A. Legasse, M. Fischer, C. Shriver-Munsch, T. Swanson, A. Sylwester, S. Hagen, E. McDonald, K. Randall, and K. Rothstein for technical or administrative assistance; B. Keele (Frederick National Laboratory) for providing the SIVmac239 challenge virus; A. Townsend for figure preparation; Oregon Health & Science University (OHSU) Massively Parallel Sequencing Shared Resource and the ONPRC Molecular Technologies Core for sequencing; and the ONPRC Molecular Virology Core for virus stock preparation. This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID grants P01 AI094417, U19 AI128741, UM1 AI124377, and R37 AI054292 to L.J.P.; grant R01 AI40888 to J.B.S.; and grant R01 AI059457 to K.F.); the National Institutes of Health, Office of the Director (core grant P51 OD011092 to the Oregon National Primate Research Center and grant U42 OD023038 to M.K.A.); and the National Cancer Institute (grant HHSN261200800001E to J.D.L.). This work was also supported by the Bill & Melinda Gates Foundation-supported Collaboration for AIDS Vaccine Discovery (grant OPP1033121 to L.J.P.). Publisher Copyright: {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",
year = "2021",
month = apr,
day = "30",
doi = "10.1126/science.abe9233",
language = "English (US)",
volume = "372",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6541",
}