Cytomegalovirus-vaccine-induced unconventional T cell priming and control of SIV replication is conserved between primate species

Author:

Malouli, Daniel

Gilbride, Roxanne M

Wu, Helen L

Hwang, Joseph M

Maier, Nicholas

Hughes, Colette M

Newhouse, Daniel

Morrow, David

Ventura, Abigail B

Law, Lynn

Tisoncik-Go, Jennifer

Whitmore, Leanne

Smith, Elise

Golez, Inah

Chang, Jean

Reed, Jason S

Waytashek, Courtney

Weber, Whitney

Taher, Husam

Uebelhoer, Luke S

Womack, Jennie L

McArdle, Matthew R

Gao, Junwei

Papen, Courtney R

Lifson,Jeffrey

Burwitz, Benjamin J

Axthelm, Michael K

Smedley, Jeremy

Früh, Klaus

Gale, Michael

Picker, Louis J

Hansen, Scott G

Sacha, Jonah B
Author Address

Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA., Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington, Seattle, WA 98109, USA., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA. Electronic address: hansensc@ohsu.edu., 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.,

Abstract:

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. Copyright © 2022 Elsevier Inc. All rights reserved.

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