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

Abstract

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.

• Authors: Susan E Murray, Pavlo A Nesterenko, Adam L Vanarsdall, Michael W Munks, Savannah M Smart, Eren M Veziroglu, Lavinia C Sagario, Ronzo Lee, Frans H J Claas, Ilias I N Doxiadis, Michael A McVoy, Stuart P Adler, Ann B Hill
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 214 Issue 7 Pg. 1889-1899 (Jul 03 2017) ISSN: 1540-9538 [Electronic] United States
• PMID: 28566275 (Publication Type: Clinical Trial, Phase I, Journal Article)
• Copyright: © 2017 Murray et al.

Chemical References

• Cytomegalovirus Vaccines
• Epitopes
• Histocompatibility Antigens Class I

Topics

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