Immunotherapy and Vaccination After Transplant: The Present, the Future

Emery, Vincent C.; Einsele, Hermann; Atabani, Sowsan; Haque, Tanzina

doi:10.1016/j.idc.2010.01.004

Cited by 5 publications

(3 citation statements)

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“…Thus, there is a need for safer and more efficient alternatives. All components of the adaptive immune system, B cells, CD4 + T helper cells (Th), and CD8 + cytotoxic T cells (CTLs)[2], [13], [14], [15], are involved in generating and maintaining anti-HCMV immunity, and it is believed that vaccination and/or immunotherapy may provide efficient prevention and/or treatment without side effects[16], [17], [18]. In particular, trials with adoptive T cell transfer of HCMV-specific T cells to recipients of allo-HCT have been encouraging[19], [20], [21], [22].…”

Section: Introductionmentioning

confidence: 99%

Identification and HLA-Tetramer-Validation of Human CD4+ and CD8+ T Cell Responses against HCMV Proteins IE1 and IE2

et al. 2014

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Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.

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Section: Introductionmentioning

confidence: 99%

Identification and HLA-Tetramer-Validation of Human CD4+ and CD8+ T Cell Responses against HCMV Proteins IE1 and IE2

et al. 2014

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“…Increased serum levels of sCD30 have been found in IM patients compared to the healthy controls [Vinante et al, 1994]. EBV is also associated with lymphoid tumors such as a subset of Hodgkin's lymphoma and lymphoproliferative diseases in immunocompromised patients, in particular in transplant patients (post‐transplant lymphoproliferative disease, PTLD) [Emery et al, 2010]. PTLD is a recognized complication of immunosuppression affecting up to 10% of transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

Soluble CD30: A serum marker for Epstein-Barr virus-associated lymphoproliferative diseases

Haque¹,

Chaggar²,

Schafers³

et al. 2010

J. Med. Virol.

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 The soluble form of CD30 (sCD30), a member of tumour necrosis factor receptor superfamily, has been used as a marker of disease activity in various lymphomas. EpsteinBarr virus (EBV) is a potent stimulator of CD30 expression. The study aims to evaluate whether sCD30 can be used as a diagnostic marker for EBV-associated infectious mononucleosis (IM) and post-transplant lymphoproliferative disease (PTLD). Plasma from EBV seropositive healthy controls (N=90), acute IM patients (n=90), non-PTLD heart/lung transplant recipients (N=30) and EBV-positive PTLD patients (N=23) was tested for sCD30 using a commercially available ELISA kit. EBV DNA was tested by real time quantitative polymerase chain reaction assay. Significantly higher sCD30 levels were observed in acute IM patients (median 242.9 ng/mL) compared to EBV seropositive controls (median 15.7 ng/mL; p<0.0001). These levels were highest in IM patients within 14 days of onset of illness.PTLD patients had significantly higher sCD30 levels (median 94 ng/mL) than healthy controls (p<0.0001) and transplant patients (median 27 ng/mL; p=0.0007). EBV DNA was detected mostly in acute IM and PTLD patients. In both cases there was a significant correlation between sCD30 and EBV DNA levels in plasma (p<0.0001). This study demonstrates that sCD30 and EBV DNA levels can be used as potential markers for diagnosis of IM and PTLD.

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“…the residual immune system still retains functionality after SOT which contributes to CMV control and the availability of CMV prophylactic drugs such as valganciclovir minimizes CMV disease risks further . In contrast, EBV infection and in particular EBV‐driven PTLD is a more difficult disease to manage with little evidence that antiherpes drugs are effective especially once PTLD is manifest (reviewed in ). Guidelines are available for the management of PTLD posttransplantation (e.g.…”

Section: Adoptive Immunotherapeutic Developmentsmentioning

confidence: 99%

Human Herpesvirus Vaccines and Future Directions

Emery

2013

American Journal of Transplantation

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Over the last few years there has been an impressive increase in the virological and immunological tools available to detect both human herpesvirus (HHV) and immune control of replication post-solid organ transplantation. This has allowed a greater appreciation of pathogenesis, studies to be designed to evaluate potential vaccines, new approaches adopted for antiviral deployment and the success of interventions to be judged. This chapter aims to summarize the state-ofthe-art in vaccine development and look forward to the role that vaccines, immune monitoring, viral kinetics and new antiherpesvirus agents may play in the future management of HHV infections after transplantation. Key words: Adoptive immunotherapy, antiviral drugs, immune responses, oka vaccine, viral kineticsAbbreviations: ADCC, antibody-dependent cellular cytotoxicity; CMV, cytomegalovirus; CTL, cytotoxic T lymphocytes; EBV, Epstein-Barr virus; gB CMV, glycoprotein B; GCV, ganciclovir; HHV, human herpesviruses; HSV, herpes simplex virus; IE, immediate early; IFN, interferon; IL, interleukin; od, once a day dosing; PTLD, posttransplant lymphoproliferative disease; pp65, the pp65 phosphoprotein of CMV-also known as ppUL83; R0, basic reproductive number; SCT, stem cell transplantation; SOT, solid organ transplantation; TNF, tumor necrosis factor; VGCV, valganciclovir; VZV, varicella zoster virus.

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Immunotherapy and Vaccination After Transplant: The Present, the Future

Cited by 5 publications

References 86 publications

Identification and HLA-Tetramer-Validation of Human CD4+ and CD8+ T Cell Responses against HCMV Proteins IE1 and IE2

Identification and HLA-Tetramer-Validation of Human CD4+ and CD8+ T Cell Responses against HCMV Proteins IE1 and IE2

Soluble CD30: A serum marker for Epstein-Barr virus-associated lymphoproliferative diseases

Human Herpesvirus Vaccines and Future Directions

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