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

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 2017;214(7):1889-1899

PMID: 28566275

Free Full Text on PubMed Central View on PubMed

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.

Address: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR.; Department of Biology, University of Portland, Portland, OR.; Department of Pediatrics, Virginia Commonwealth University, Richmond, VA.; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.; CMV Research Foundation, Inc., Richmond, VA.; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR [email protected].

DOI: 10.1084/jem.20161988