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

• Published in: The Journal of experimental medicine Vol. 214; no. 7; pp. 1889 - 1899
• Main Authors: Murray, Susan E, Nesterenko, Pavlo A, Vanarsdall, Adam L, Munks, Michael W, Smart, Savannah M, Veziroglu, Eren M, Sagario, Lavinia C, Lee, Ronzo, Claas, Frans H J, Doxiadis, Ilias I N, McVoy, Michael A, Adler, Stuart P, Hill, Ann B
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 03.07.2017; The Rockefeller University Press
• Subjects: Acquired immune deficiency syndrome; AIDS; Amino Acid Sequence; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cell Line, Tumor; Cells, Cultured; Cytomegalovirus; 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; Fibroblasts - immunology; Fibroblasts - virology; Flow Cytometry; Herpesviridae; Histocompatibility antigen HLA; Histocompatibility Antigens Class I - immunology; Host-Pathogen Interactions - drug effects; Host-Pathogen Interactions - immunology; Human behavior; Human cytomegalovirus; Human subjects; Humans; K562 Cells; Lentivirus; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; Lymphocytes; Lymphocytes T; Macaca mulatta; Major histocompatibility complex; Male; Microscopy, Fluorescence; Monkeys; Mutation; Retroviridae; T cell receptors; Tropism; Vaccination; Vaccines; Viruses
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20161988

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.