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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.

SUBMITTER: Murray SE 

PROVIDER: S-EPMC5502433 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Murray Susan E SE   Nesterenko Pavlo A PA   Vanarsdall Adam L AL   Munks Michael W MW   Smart Savannah M SM   Veziroglu Eren M EM   Sagario Lavinia C LC   Lee Ronzo R   Claas Frans H J FHJ   Doxiadis Ilias I N IIN   McVoy Michael A MA   Adler Stuart P SP   Hill Ann B AB  

The Journal of experimental medicine 20170531 7


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 t  ...[more]

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