@article{d0de7d5554f84cd2bad683f80ebcce26,
title = "Cytomegalovirus-vaccine-induced unconventional T cell priming and control of SIV replication is conserved between primate species",
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.",
keywords = "HIV, T cells, vaccine",
author = "Daniel Malouli and Gilbride, {Roxanne M.} and Wu, {Helen L.} and Hwang, {Joseph M.} and Nicholas Maier and Hughes, {Colette M.} and Daniel Newhouse and David Morrow and Ventura, {Abigail B.} and Lynn Law and Jennifer Tisoncik-Go and Leanne Whitmore and Elise Smith and Inah Golez and Jean Chang and Reed, {Jason S.} and Courtney Waytashek and Whitney Weber and Husam Taher and Uebelhoer, {Luke S.} and Womack, {Jennie L.} and McArdle, {Matthew R.} and Junwei Gao and Papen, {Courtney R.} and Lifson, {Jeffrey D.} and Burwitz, {Benjamin J.} and Axthelm, {Michael K.} and Jeremy Smedley and Klaus Fr{\"u}h and Michael Gale and Picker, {Louis J.} and Hansen, {Scott G.} and Sacha, {Jonah B.}",
note = "Funding Information: We thank Dr. Ulrich Koszinowski for providing BAC plasmid pHA1; Drs. Nancy Haigwood, Ann Hessell, and William Sutton for assistance with enzyme-linked immunosorbent assays (ELISAs); Dr. Rebecca Agnor for statistical analysis; and staff at the Quantitative Molecular Diagnostics Core of the AIDS and Cancer Virus Program. The following reagents were obtained through the NIH HIV Reagent Program: SIVmac251 pr55 Gag Protein, and Peptide Arrays, SIVmac239 Gag, Tat, Rev, Nef, Vif, and Env. This work was supported by R01 AI129703 to J.B.S. R01 AI140888 to J.B.S. and S.G.H. P51 OD011092 from the NIH Office of the Director to the Oregon National Primate Research Center (P51 Core grant), contract HHSN272201800008C to M.G. the NIH Office of the Director to the Washington National Primate Research Center P51 Core grant OD010425, and in part with federal funds from the National Cancer Institute under contract nos. HHSN261200800001E and 75N91019D00024 to J.D.L. D. Malouli and H.L.W. isolated CyCMV, and D. Malouli, L.S.U. J.L.W. M.R.M. J.G. C.R.P. and H.T. BAC captured, constructed, and validated all RhCMV and CyCMV vectors with supervision from K.F. S.G.H. planned and performed animal experiments and performed and analyzed immunologic assays, assisted by A.B.V. D. Morrow, B.J.B. R.M.G. N.M. C.M.H. J.S.R. and W.W. J.M.H. planned and performed the ELISA assays. M.K.A. and J.S. managed the animal care and procedures. J.D.L. supervised SIV quantification. D.N. L.L. J.G. L.W. I.G. J.C. and E.S. processed and analyzed transcriptomic experiments supervised by M.G. J.B.S. conceived and supervised all experiments, acquired funding, analyzed and interpreted data, and wrote the paper, assisted by S.G.H. K.F. L.J.P. and M.G. OHSU and Drs. Malouli, Fr{\"u}h, Picker, Hansen, and Sacha have a significant financial interest in Vir Biotechnology, Inc. a company that may have a financial interest in the results of this research and technology. This potential individual and institutional conflict of interest has been reviewed and managed by OHSU. Funding Information: We thank Dr. Ulrich Koszinowski for providing BAC plasmid pHA1; Drs. Nancy Haigwood, Ann Hessell, and William Sutton for assistance with enzyme-linked immunosorbent assays (ELISAs); Dr. Rebecca Agnor for statistical analysis; and staff at the Quantitative Molecular Diagnostics Core of the AIDS and Cancer Virus Program. The following reagents were obtained through the NIH HIV Reagent Program: SIVmac251 pr55 Gag Protein, and Peptide Arrays, SIVmac239 Gag, Tat, Rev, Nef, Vif, and Env. This work was supported by R01 AI129703 to J.B.S., R01 AI140888 to J.B.S. and S.G.H., P51 OD011092 from the NIH Office of the Director to the Oregon National Primate Research Center (P51 Core grant), contract HHSN272201800008C to M.G., the NIH Office of the Director to the Washington National Primate Research Center P51 Core grant OD010425 , and in part with federal funds from the National Cancer Institute under contract nos. HHSN261200800001E and 75N91019D00024 to J.D.L. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = sep,
day = "14",
doi = "10.1016/j.chom.2022.07.013",
language = "English (US)",
volume = "30",
pages = "1207--1218.e7",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "9",
}