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

Susan Murray, Pavlo A. Nesterenko, Adam Vanarsdall, Michael 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 Hill

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16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1889-1899
Number of pages11
JournalJournal of Experimental Medicine
Volume214
Issue number7
DOIs
StatePublished - Jul 1 2017

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Murray, S., Nesterenko, P. A., Vanarsdall, A., Munks, M., Smart, S. M., Veziroglu, E. M., Sagario, L. C., Lee, R., Claas, F. H. J., Doxiadis, I. I. N., McVoy, M. A., Adler, S. P., & Hill, A. (2017). Fibroblast-adapted human CMV vaccines elicit predominantly conventional CD8 T cell responses in humans. Journal of Experimental Medicine, 214(7), 1889-1899. https://doi.org/10.1084/jem.20161988