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; 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.