Cytomegalovirus-vaccine-induced unconventional T cell priming and control of SIV replication is conserved between primate species.
Daniel Malouli, Roxanne M Gilbride, Helen L Wu, Joseph M Hwang, Nicholas Maier, Colette M Hughes, Daniel Newhouse, David Morrow, Abigail B Ventura, Lynn Law, Jennifer Tisoncik-Go, Leanne Whitmore, Elise Smith, Inah Golez, Jean Chang, Jason S Reed, Courtney Waytashek, Whitney Weber, Husam Taher, Luke S Uebelhoer, Jennie L Womack, Matthew R McArdle, Junwei Gao, Courtney R Papen, Jeffrey D Lifson, Benjamin J Burwitz, Michael K Axthelm, Jeremy Smedley, Klaus Früh, Michael Gale, Louis J Picker, Scott G Hansen, Jonah B Sacha
Author Information
Daniel Malouli: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Roxanne M Gilbride: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Helen L Wu: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Joseph M Hwang: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Nicholas Maier: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Colette M Hughes: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Daniel Newhouse: Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
David Morrow: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Abigail B Ventura: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Lynn Law: Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Jennifer Tisoncik-Go: Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Leanne Whitmore: Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Elise Smith: Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Inah Golez: Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Jean Chang: Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Jason S Reed: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Courtney Waytashek: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Whitney Weber: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Husam Taher: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Luke S Uebelhoer: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Jennie L Womack: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Matthew R McArdle: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Junwei Gao: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Courtney R Papen: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Jeffrey D Lifson: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Benjamin J Burwitz: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Michael K Axthelm: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Jeremy Smedley: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Klaus Früh: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Michael Gale: Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Louis J Picker: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.
Scott G Hansen: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA. Electronic address: hansensc@ohsu.edu.
Jonah B Sacha: Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, 97006, USA. Electronic address: sacha@ohsu.edu.
Strain 68-1 rhesus cytomegalovirus expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) primes MHC-E-restricted CD8+ T cells that control SIV replication in 50%-60% of the vaccinated rhesus macaques. Whether this unconventional SIV-specific immunity and protection is unique to rhesus macaques or RhCMV or is intrinsic to CMV remains unknown. Here, using cynomolgus CMV vectors expressing SIV antigens (CyCMV/SIV) and Mauritian cynomolgus macaques, we demonstrate that the induction of MHC-E-restricted CD8+ T cells requires matching CMV to its host species. RhCMV does not elicit MHC-E-restricted CD8+ T cells in cynomolgus macaques. However, cynomolgus macaques vaccinated with species-matched 68-1-like CyCMV/SIV mounted MHC-E-restricted CD8+ T cells, and half of the vaccinees stringently controlled SIV post-challenge. Protected animals manifested a vaccine-induced IL-15 transcriptomic signature that is associated with efficacy in rhesus macaques. These findings demonstrate that the ability of species-matched CMV vectors to elicit MHC-E-restricted CD8+ T cells that are required for anti-SIV efficacy is conserved in nonhuman primates, and these data support the development of HCMV/HIV for a prophylactic HIV vaccine.
