Varicella-zoster virus glycoproteins B and E are major targets of CD4+ and CD8+ T cells reconstituting during zoster after allogeneic transplantation.
BACKGROUND
After allogeneic hematopoietic stem-cell transplantation patients are at increased risk for herpes zoster as long as varicella-zoster virus specific T-cell reconstitution is impaired. This study aimed to identify immunodominant varicella-zoster virus antigens that drive recovery of virus-specific T cells after transplantation.


METHODS
Antigens were purified from a varicella-zoster virus infected cell lysate by high-performance liquid chromatography and were identified by quantitative mass spectrometric analysis. To approximate in vivo immunogenicity for memory T cells, antigen preparations were consistently screened with ex vivo PBMC of varicella-zoster virus immune healthy individuals in sensitive interferon-γ ELISpot assays. Candidate virus antigens identified by the approach were genetically expressed in PBMC using electroporation of in vitro transcribed RNA encoding full-length proteins and were then analyzed for recognition by CD4(+) and CD8(+) memory T cells.


RESULTS
Varicella-zoster virus encoded glycoproteins B and E, and immediate early protein 62 were identified in immunoreactive lysate material. Predominant CD4(+) T-cell reactivity to these proteins was observed in healthy virus carriers. Furthermore, longitudinal screening in allogeneic stem-cell transplantation patients showed strong expansions of memory T cells recognizing glycoproteins B and E after onset of herpes zoster, while immediate early protein 62 reactivity remained moderate. Reactivity to viral glycoproteins boosted by acute zoster was mediated by both CD4(+) and CD8(+) T cells.


CONCLUSIONS
Our data demonstrate that glycoproteins B and E are major targets of varicella-zoster virus specific CD4(+) and CD8(+) T-cell reconstitution occurring during herpes zoster after allogeneic stem-cell transplantation. Varicella-zoster virus glycoproteins B and E might form the basis for novel non-hazardous zoster subunit vaccines suitable for immunocompromised transplant patients.
Department of Medicine III, University Medical Center, Mainz, Germany.
Patrick
P
Kleemann
Eva
E
Distler
Eva M
EM
Wagner
Simone
S
Thomas
Sebastian
S
Klobuch
Steffi
S
Aue
Elke
E
Schnürer
Hansjörg
H
Schild
Matthias
M
Theobald
Bodo
B
Plachter
Stefan
S
Tenzer
Ralf G
RG
Meyer
Wolfgang
W
Herr
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018274:Electroporation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006562:Herpes Zoster / Q000276:immunology / Q000821:virology; D014645:Herpesvirus 3, Human / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008297:Male; D010957:Plasmids; D021241:Spectrometry, Mass, Electrospray Ionization; D014162:Transfection; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
D014759:Viral Envelope Proteins; C090198:glycoprotein B, varicella-zoster virus