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


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.

DOI: 10.1084/jem.20161988

Cite this paper

@article{Murray2017FibroblastadaptedHC, title={Fibroblast-adapted human CMV vaccines elicit predominantly conventional CD8 T cell responses in humans.}, author={Susan Murray and Pavlo A Nesterenko and Adam L. Vanarsdall and Michael W Munks and Savannah M. Smart and Eren M Veziroglu and Lavinia C Sagario and Ronzo B. Lee and Franz H J Claas and Ilias I N Doxiadis and Michael A. McVoy and Stuart P. Adler and Ann B Hill}, journal={The Journal of experimental medicine}, year={2017}, volume={214 7}, pages={1889-1899} }