Fibroblast-adapted human CMV vaccines elicit predominantly conventional CD8 T cell responses in humans

J Exp Med. 2017 Jul 3;214(7):1889-1899. doi: 10.1084/jem.20161988. Epub 2017 May 31.


Cytomegalovirus (CMV)-based vaccines have shown remarkable efficacy in the rhesus macaque model of acquired immune deficiency syndrome, enabling 50% of vaccinated monkeys to clear a subsequent virulent simian immunodeficiency virus challenge. The protective vaccine elicited unconventional CD8 T cell responses that were entirely restricted by MHC II or the nonclassical MHC I molecule, MHC-E. These unconventional responses were only elicited by a fibroblast-adapted rhesus CMV vector with limited tissue tropism; a repaired vector with normal tropism elicited conventional responses. Testing whether these unusual protective CD8 T responses could be elicited in humans requires vaccinating human subjects with a fibroblast-adapted mutant of human CMV (HCMV). In this study, we describe the CD8 T cell responses of human subjects vaccinated with two fibroblast-adapted HCMV vaccines. Most responses were identified as conventional classically MHC I restricted, and we found no evidence for MHC II or HLA-E restriction. These results indicate that fibroblast adaptation alone is unlikely to explain the unconventional responses observed in macaques.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Amino Acid Sequence
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / prevention & control
  • Cytomegalovirus Infections / virology
  • Cytomegalovirus Vaccines / administration & dosage
  • Cytomegalovirus Vaccines / genetics
  • Cytomegalovirus Vaccines / immunology*
  • Epitopes / immunology
  • Fibroblasts / immunology*
  • Fibroblasts / virology
  • Flow Cytometry
  • Histocompatibility Antigens Class I / immunology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • K562 Cells
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Male
  • Microscopy, Fluorescence
  • Mutation
  • Vaccination


  • Cytomegalovirus Vaccines
  • Epitopes
  • Histocompatibility Antigens Class I

Associated data

  • GENBANK/KX101021
  • GENBANK/KX101022
  • GENBANK/KX101023
  • GENBANK/KX101024