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...

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Published inThe Journal of experimental medicine Vol. 214; no. 7; pp. 1889 - 1899
Main Authors Murray, Susan E., Nesterenko, Pavlo A., Vanarsdall, Adam L., Munks, Michael W., Smart, Savannah M., Veziroglu, Eren M., Sagario, Lavinia C., Lee, Ronzo, Claas, Frans H.J., Doxiadis, Ilias I.N., McVoy, Michael A., Adler, Stuart P., Hill, Ann B.
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 03.07.2017
The Rockefeller University Press
Subjects
Acquired immune deficiency syndrome
AIDS
Amino Acid Sequence
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell Line
Cell Line, Tumor
Cells, Cultured
Cytomegalovirus
Cytomegalovirus - immunology
Cytomegalovirus - physiology
Cytomegalovirus Infections - immunology
Cytomegalovirus Infections - prevention & control
Cytomegalovirus Infections - virology
Cytomegalovirus Vaccines - administration & dosage
Cytomegalovirus Vaccines - genetics
Cytomegalovirus Vaccines - immunology
Epitopes - immunology
Fibroblasts
Fibroblasts - immunology
Fibroblasts - virology
Flow Cytometry
Herpesviridae
Histocompatibility antigen HLA
Histocompatibility Antigens Class I - immunology
Host-Pathogen Interactions - drug effects
Host-Pathogen Interactions - immunology
Human behavior
Human cytomegalovirus
Human subjects
Humans
K562 Cells
Lentivirus
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - virology
Lymphocytes
Lymphocytes T
Macaca mulatta
Major histocompatibility complex
Male
Microscopy, Fluorescence
Monkeys
Mutation
Retroviridae
T cell receptors
Tropism
Vaccination
Vaccines
Viruses
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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.
AbstractList Fibroblast-adapted rhesus CMV-vectored vaccines protect macaques from SIV challenge and elicit unconventional CD8 T cell responses. In contrast, Murray et al. show that humans vaccinated with fibroblast-adapted human CMV vaccines generate conventional CD8 T cell responses. 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.
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.
Fibroblast-adapted rhesus CMV–vectored vaccines protect macaques from SIV challenge and elicit unconventional CD8 T cell responses. In contrast, Murray et al. show that humans vaccinated with fibroblast-adapted human CMV vaccines generate conventional CD8 T cell responses. 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.
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.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.
Author Nesterenko, Pavlo A.
Veziroglu, Eren M.
Murray, Susan E.
Hill, Ann B.
Doxiadis, Ilias I.N.
Adler, Stuart P.
Sagario, Lavinia C.
Lee, Ronzo
Munks, Michael W.
Smart, Savannah M.
Claas, Frans H.J.
McVoy, Michael A.
Vanarsdall, Adam L.
AuthorAffiliation 2 Department of Biology, University of Portland, Portland, OR
1 Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR
4 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
3 Department of Pediatrics, Virginia Commonwealth University, Richmond, VA
5 CMV Research Foundation, Inc., Richmond, VA
AuthorAffiliation_xml – name: 3 Department of Pediatrics, Virginia Commonwealth University, Richmond, VA
– name: 4 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
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S.E. Murray and P.A. Nesterenko contributed equally to this paper.
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Snippet Cytomegalovirus (CMV)-based vaccines have shown remarkable efficacy in the rhesus macaque model of acquired immune deficiency syndrome, enabling 50% of...
Fibroblast-adapted rhesus CMV–vectored vaccines protect macaques from SIV challenge and elicit unconventional CD8 T cell responses. In contrast, Murray et al....
Fibroblast-adapted rhesus CMV-vectored vaccines protect macaques from SIV challenge and elicit unconventional CD8 T cell responses. In contrast, Murray et al....
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SubjectTerms Acquired immune deficiency syndrome
AIDS
Amino Acid Sequence
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell Line
Cell Line, Tumor
Cells, Cultured
Cytomegalovirus
Cytomegalovirus - immunology
Cytomegalovirus - physiology
Cytomegalovirus Infections - immunology
Cytomegalovirus Infections - prevention & control
Cytomegalovirus Infections - virology
Cytomegalovirus Vaccines - administration & dosage
Cytomegalovirus Vaccines - genetics
Cytomegalovirus Vaccines - immunology
Epitopes - immunology
Fibroblasts
Fibroblasts - immunology
Fibroblasts - virology
Flow Cytometry
Herpesviridae
Histocompatibility antigen HLA
Histocompatibility Antigens Class I - immunology
Host-Pathogen Interactions - drug effects
Host-Pathogen Interactions - immunology
Human behavior
Human cytomegalovirus
Human subjects
Humans
K562 Cells
Lentivirus
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - virology
Lymphocytes
Lymphocytes T
Macaca mulatta
Major histocompatibility complex
Male
Microscopy, Fluorescence
Monkeys
Mutation
Retroviridae
T cell receptors
Tropism
Vaccination
Vaccines
Viruses
Title Fibroblast-adapted human CMV vaccines elicit predominantly conventional CD8 T cell responses in humans
URI https://www.ncbi.nlm.nih.gov/pubmed/28566275
https://www.proquest.com/docview/1983433423
https://www.proquest.com/docview/1904907022
https://www.proquest.com/docview/1919975863
https://pubmed.ncbi.nlm.nih.gov/PMC5502433
Volume 214
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