Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy
Marieke C. Verweij, Scott G. Hansen, Ravi Iyer, Nessy John, Daniel Malouli, David Morrow, Isabel Scholz, Jennie Womack, Shaheed Abdulhaqq, Roxanne M. Gilbride, Colette M. Hughes, Abigail B. Ventura, Julia C. Ford, Andrea N. Selseth, Kelli Oswald, Rebecca Shoemaker, Brian Berkemeier, William J. Bosche, Michael Hull, Jason Shao, Jonah B. Sacha, Michael K. Axthelm, Paul T. Edlefsen, Jeffrey D. Lifson, Louis J. Picker, Klaus Früh
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