Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy

Marieke C. Verweij(Oregon National Primate Research Center), Scott G. Hansen(Oregon National Primate Research Center), Ravi Iyer(Oregon National Primate Research Center), Nessy John(Oregon National Primate Research Center), Daniel Malouli(Oregon National Primate Research Center), David Morrow(Oregon National Primate Research Center), Isabel Scholz(Oregon National Primate Research Center), Jennie Womack(Oregon National Primate Research Center), Shaheed Abdulhaqq(Oregon National Primate Research Center), Roxanne M. Gilbride(Oregon National Primate Research Center), Colette M. Hughes(Oregon National Primate Research Center), Abigail B. Ventura(Oregon National Primate Research Center), Julia C. Ford(Oregon National Primate Research Center), Andrea N. Selseth(Oregon National Primate Research Center), Kelli Oswald(Frederick National Laboratory for Cancer Research), Rebecca Shoemaker(Frederick National Laboratory for Cancer Research), Brian Berkemeier(Frederick National Laboratory for Cancer Research), William J. Bosche(Frederick National Laboratory for Cancer Research), Michael Hull(Frederick National Laboratory for Cancer Research), Jason Shao(Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa), Jonah B. Sacha(Oregon National Primate Research Center), Michael K. Axthelm(Oregon National Primate Research Center), Paul T. Edlefsen(Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa), Jeffrey D. Lifson(Frederick National Laboratory for Cancer Research), Louis J. Picker(Oregon National Primate Research Center), Klaus Früh(Oregon National Primate Research Center)
Science
March 25, 2021
10.1126/science.abe9233
Cited by 60Open Access
Full Text

Abstract

Viral peptide is key to T cell priming Simian immunodeficiency virus (SIV) vaccines containing a strain 68-1 rhesus cytomegalovirus (RhCMV) vector elicit strong CD8 + T cell responses that can control and clear SIV infections. The SIV peptides targeted by these T cells are presented on major histocompatibility complex (MHC) II and the nonclassical MHC-Ib molecule MHC-E rather than the more typical MHC-Ia. Verweij et al. show that the 68-1 RhCMV–encoded peptide VL9 drives intracellular transport of MHC-E and recognition of RhCMV-infected targets by MHC-E–restricted CD8 + T cells. Rhesus macaques vaccinated with a mutant 68-1 RhCMV lacking VL9 showed no priming of MHC-E–restricted CD8 + T cells and no protection against SIV. This work strongly suggests that future effective CMV-based HIV vaccines in humans will also require MHC-E–restricted CD8 + T cell priming. Science , this issue p. eabe9233

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