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. UebelhoerJennie 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1207-1218.e7
JournalCell Host and Microbe
Volume30
Issue number9
DOIs
StatePublished - Sep 14 2022

Keywords

  • HIV
  • T cells
  • vaccine

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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