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Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Tropical and other Infectious Diseases".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 29686

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Prof. Dr. Oliver Witzke

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Guest Editor

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
Interests: infectious diseases; herpesviruses; infections in immunosuppressed hosts; immunomonitoring; biomarker

Dr. Adalbert Krawczyk

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Guest Editor

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany
Interests: antiviral antibodies; antiviral therapy and resistance; herpes simplex viruses; human cytomegalovirus; SARS-CoV-2
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Special Issue Information

Dear Colleagues,

Herpesviruses are globally distributed and belong to the most common viruses that affect humans. Most of us are infected with at least one of the eight human herpesviruses. These include herpes simplex virus type 1 and 2, varicella-zoster virus, Epstein–Barr-virus, human cytomegalovirus, human herpesviruses 6 and 7, and Kaposi’s sarcoma-associated herpesvirus (HHV-8). Upon primary infection, herpesviruses persist latently in the host. Herpesviruses are well adapted to their hosts and remain lifelong under the control of the immune system without causing serious disease.

However, herpesviruses may cause severe, even life-threatening disease in high-risk individuals, such as intensive care patients, HIV-infected people with AIDS, cancer patients, and in solid organ or bone marrow transplants. Mostly, severe diseases occur when the host’s immunity is compromised due to aging, co-infections, or another underlying disease. Understanding the risk factors associated with a more severe course of the disease will help to improve prophylactic and therapeutic interventions against these viruses.

We highly encourage the submission of articles to this Special Issue, which will contribute to a better understanding of the risk factors that are associated with a higher frequency of reactivations or a more severe disease. Furthermore, we accept manuscripts describing the herpesvirus-specific immunomonitoring in patient groups of increased risk.

Identification of novel vaccine candidates or therapeutics, which can protect from disease or suppress the virus replication is important, articles on this topic are also welcome.

Prof. Dr. Oliver Witzke
Dr. Adalbert Krawczyk
Guest Editors

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Keywords

herpes simplex type 1
herpes simplex type 2
human cytomegalovirus
human herpesvirus 6
human herpesvirus 8
transplantation
risk for a severe course of the disease

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Published Papers (9 papers)

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Research

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17 pages, 5178 KiB

Open AccessArticle

Cellular Immune Response after Vaccination with an Adjuvanted, Recombinant Zoster Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients

by Michael Koldehoff, Peter A. Horn and Monika Lindemann

Vaccines 2022, 10(5), 809; https://doi.org/10.3390/vaccines10050809 - 20 May 2022

Cited by 13 | Viewed by 3178

Abstract

Hematopoietic stem cell transplant (HSCT) recipients have a high risk of developing primary varicella-zoster virus (VZV) infection and reactivation. VZV vaccination may prevent infection and reactivation. In the current study, recipients of allogeneic HSCT (34 females, 45 males) were vaccinated with adjuvanted, recombinant zoster vaccine Shingrix™, which contains the VZV glycoprotein E. Cellular immunity against various VZV antigens was analyzed by interferon-gamma ELISpot. Peripheral blood mononuclear cells (PBMC) of recipients with versus without prior shingles (n = 36 and n = 43, respectively) showed approximately twofold higher VZV-specific responses prior to and post vaccination. After the first and second vaccination, ELISpot responses towards the glycoprotein E were significantly higher in males versus females (median of spots increment 18 versus 1 and 17 versus 4, respectively, p ≤ 0.02 each). Multivariate analysis showed that shingles and sex both impacts significantly on VZV immunity. Whereas vaccination-induced changes could hardly be detected after stimulation with a whole VZV antigen, there was a significant increase in responses towards glycoprotein E after vaccination (p < 0.005). These data indicate that vaccination with Shingrix™ augmented cellular, VZV-specific immunity in HSCT recipients. Shingles and male sex could both be identified as factors leading to increased immunity. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

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18 pages, 3192 KiB

Open AccessFeature PaperArticle

HSV-1 ICP22 Is a Selective Viral Repressor of Cellular RNA Polymerase II-Mediated Transcription Elongation

by Nur Firdaus Isa, Olivier Bensaude, Nadiah C. Aziz and Shona Murphy

Vaccines 2021, 9(10), 1054; https://doi.org/10.3390/vaccines9101054 - 22 Sep 2021

Cited by 19 | Viewed by 4437 | Correction

Abstract

The Herpes Simplex Virus (HSV-1) immediate-early protein ICP22 interacts with cellular proteins to inhibit host cell gene expression and promote viral gene expression. ICP22 inhibits phosphorylation of Ser2 of the RNA polymerase II (pol II) carboxyl-terminal domain (CTD) and productive elongation of pol II. Here we show that ICP22 affects elongation of pol II through both the early-elongation checkpoint and the poly(A)-associated elongation checkpoint of a protein-coding gene model. Coimmunoprecipitation assays using tagged ICP22 expressed in human cells and pulldown assays with recombinant ICP22 in vitro coupled with mass spectrometry identify transcription elongation factors, including P-TEFb, additional CTD kinases and the FACT complex as interacting cellular factors. Using a photoreactive amino acid incorporated into ICP22, we found that L191, Y230 and C225 crosslink to both subunits of the FACT complex in cells. Our findings indicate that ICP22 interacts with critical elongation regulators to inhibit transcription elongation of cellular genes, which may be vital for HSV-1 pathogenesis. We also show that the HSV viral activator, VP16, has a region of structural similarity to the ICP22 region that interacts with elongation factors, suggesting a model where VP16 competes with ICP22 to deliver elongation factors to viral genes. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

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7 pages, 240 KiB

Open AccessCommunication

Risk Factors for Herpes Zoster in Patients with Chronic Kidney Disease: A Case-Control Study

by Zhenxing Li, Qiao Wang, Jiahui Ma, Zhi Li, Dong Huang, Yuzhao Huang and Haocheng Zhou

Vaccines 2021, 9(9), 963; https://doi.org/10.3390/vaccines9090963 - 28 Aug 2021

Cited by 8 | Viewed by 3593

Abstract

(1) Background: Chronic kidney disease (CKD) increases the susceptibility to the presence of herpes zoster (HZ). Little is known about the risk factors of HZ in CKD patients; (2) Methods: This is a case-control study. CKD patients diagnosed with HZ between January 2015 and June 2021 in a tertiary hospital were identified. One age- and gender- matched control was paired for each case, matched to the date of initial HZ diagnosis. Conditional multiple logistic regression was used to evaluate the risk factors associated with the presence of HZ; (3) Results: Forty-seven HZ patients and controls were identified. In general, about 73.40% (69 out of 94) patients were classified at IV to V stages of CKD. Immunosuppressive agents (p = 0.0012) and dialysis therapy (p = 0.021) were reported more frequently in the HZ cohort. Compared with the control group, the total white cell count and lymphocyte count were significantly lower in the HZ group (p value of 0.032 and 0.003, respectively). The conditional logistics regression model revealed that previous immunosuppressants administration (odds ratio: 10.861, 95% CI: 2.092~56.392, p = 0.005) and dialysis therapy (odds ratio: 3.293, 95% CI: 1.047~10.355, p = 0.041) were independent risk factors of HZ in the CKD population; (4) Conclusions: Dialysis and immunosuppressants therapy were associated with greater risk of HZ disease in CKD patients. Further guideline may highlight the necessity of zoster vaccine for patients with CKD, who undertake associated treatment. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

10 pages, 11221 KiB

Open AccessArticle

Characterization of Varicella-Zoster (VZV) Specific T Cell Response in Healthy Subjects and Transplanted Patients by Using Enzyme Linked Immunospot (ELISpot) Assays

by Irene Cassaniti, Alessandro Ferrari, Giuditta Comolli, Antonella Sarasini, Marilena Gregorini, Teresa Rampino, Daniele Lilleri and Fausto Baldanti

Vaccines 2021, 9(8), 875; https://doi.org/10.3390/vaccines9080875 - 6 Aug 2021

Cited by 7 | Viewed by 2675

Abstract

Solid organ transplant recipients, due to the administration of post-transplant immunosuppressive therapies, are at greater risk of viral reactivation episodes, mainly from herpes viruses, including varicella-zoster virus (VZV). The aim of this pilot study was to develop functional immunological assays (VZV-ELISpot) for the quantification and characterization of the VZV-specific effector-memory and central-memory responses in healthy subjects and transplanted patients. Glycoprotein gE and immediate-early 63 (IE-63) were used as antigens for in vitro stimulation. VZV-seropositive healthy subjects showed higher responses in respect to seronegative subjects. Even if differences were observed between VZV-seropositive healthy subjects and transplanted subjects at pre-transplant, the VZV-specific T-cell response was reduced at 60 days after transplant, mainly for the high level of immunosuppression. Phenotypical characterization revealed that response against VZV was mainly mediated by CD4 T cells. The results obtained in this study might be useful for the definition of personalized follow-up of the transplanted patients, providing useful information on the status of the patient potentially at risk of viral reactivation or other opportunistic infections. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

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12 pages, 755 KiB

Open AccessArticle

Association between Antiviral Prophylaxis and Cytomegalovirus and Epstein–Barr Virus DNAemia in Pediatric Recipients of Allogeneic Hematopoietic Stem Cell Transplant

by Ndeye Soukeyna Diop, Pascal Roland Enok Bonong, Chantal Buteau, Michel Duval, Jacques Lacroix, Louise Laporte, Marisa Tucci, Nancy Robitaille, Philip C. Spinella, Geoffrey Cuvelier, Suzanne M Vercauteren, Victor Lewis, Caroline Alfieri and Helen Trottier

Vaccines 2021, 9(6), 610; https://doi.org/10.3390/vaccines9060610 - 7 Jun 2021

Cited by 2 | Viewed by 2717

Abstract

Background: Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections can have serious consequences during the period of aplasia and lymphopenia following hematopoietic stem cell transplantation (HSCT). Large pediatric cohort studies examining the effect of antiviral prophylaxis against these viruses are scarce. The present study aimed to analyse the potential effect of antiviral prophylaxis (acyclovir and famciclovir) on active post-transplant EBV and CMV infection in a pediatric cohort of allogeneic HSCT recipients. Methods: We used data from the TREASuRE cohort, consisting of 156 patients who had a first allogeneic HSCT, enrolled in four pediatric centers in Canada between July 2013 and March 2017. Follow-up was performed from the time of transplant up to 100 days post-transplant. Adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the association between antiviral prophylaxis with acyclovir and/or famciclovir and EBV and CMV DNAemia was estimated using multivariate Cox regression models. Results: The post-transplant cumulative incidence of EBV and CMV DNAemia at 100 days of follow-up were, respectively, 34.5% (95% CI: 27.6–42.6) and 19.9% (95% CI: 14.5–27.1). For acyclovir, the adjusted hazard ratio (HR) for CMV and EBV DNAemia was 0.55 (95% CI: 0.24–1.26) and 1.41 (95% CI: 0.63–3.14), respectively. For famciclovir, the adjusted HR were 0.82 (95% CI: 0.30–2.29) and 0.79 (95% CI: 0.36–1.72) for CMV and EBV DNAemia, respectively. Conclusion: The antivirals famciclovir and acyclovir did not reduce the risk of post-transplant CMV and EBV DNAemia among HSCT recipients in our pediatric population. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

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14 pages, 2237 KiB

Open AccessArticle

Ageing of Immune System and Response to a Live-Attenuated Herpes Zoster Vaccine in Lung Transplant Candidates

by Lei Wang, Erik A.M. Verschuuren, Davy Paap, Christien Rondaan, Elisabeth Raveling-Eelsing, Siqi Liu, Johanna Westra and Nicolaas A. Bos

Vaccines 2021, 9(3), 202; https://doi.org/10.3390/vaccines9030202 - 28 Feb 2021

Cited by 8 | Viewed by 2474

Abstract

The mean age of lung transplant recipients has significantly increased in recent decades. Elderly recipients have a higher risk of developing herpes zoster (HZ), and they have in general a worse response to vaccination than younger persons do. We investigated the relationship between the humoral and cellular immune response to a live-attenuated HZ vaccine (Zostavax^®, Merck Sharp and Dohme) and the frequencies of T and B cell subsets, especially aged cell subsets (CD28−T cells and age associated B cells, ABCs). In total, 37 patients awaiting lung transplantation received one dose of Zostavax^®, and peripheral blood was collected before and within 6 months after vaccination. We observed a robust immune response after vaccination. The frequencies of CD28−T cells before vaccination had no impact on the subsequent immune response to HZ vaccination. However, a higher frequency of ABCs before vaccination correlated with a lower immune response especially regarding the cellular immune response. Cytomegalovirus seropositivity was associated with increased frequencies of CD28−T cells but not with frequencies of ABCs in the patients. In conclusion, increased levels of ABCs might disturb the cellular immune response to HZ vaccination, which could lower the efficacy of such vaccination in elderly transplant recipients. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

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15 pages, 1899 KiB

Open AccessArticle

Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients

by Smaranda Gliga, Melanie Fiedler, Theresa Dornieden, Anne Achterfeld, Andreas Paul, Peter A. Horn, Kerstin Herzer and Monika Lindemann

Vaccines 2021, 9(2), 88; https://doi.org/10.3390/vaccines9020088 - 25 Jan 2021

Cited by 11 | Viewed by 2747

Abstract

To estimate protection from cytomegalovirus (CMV) replication after solid organ transplantation, CMV serology has been considered insufficient and thus CMV immunity is increasingly assessed by cellular in vitro methods. We compared two commercially available IFN-γ ELISpot assays (T-Track CMV and T-SPOT.CMV) and an IFN-γ ELISA (QuantiFERON-CMV). Currently, there is no study comparing these three assays. The assays were performed in 56 liver transplant recipients at the end of antiviral prophylaxis and one month thereafter. In CMV high- or intermediate-risk patients the two ELISpot assays showed significant correlation (p < 0.0001, r > 0.6) but the correlation of the ELISpot assays with QuantiFERON-CMV was weaker. Results of both ELISpot assays were similarly predictive of protection from CMV-DNAemia ≥500 copies/mL [CMV pp65 T-SPOT.CMV at the end of prophylaxis: area under curve (AUC) = 0.744, cut-off 142 spot forming units (SFU), sensitivity set to 100%, specificity 46%; CMV IE-1 T-Track CMV at month 1: AUC = 0.762, cut-off 3.5 SFU, sensitivity set to 100%, specificity 59%]. The QuantiFERON-CMV assay was inferior, reaching a specificity of 23% when setting the sensitivity to 100%. In conclusion, both CMV-specific ELISpot assays appear suitable to assess protection from CMV infection/reactivation in liver transplant recipients. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

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Review

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28 pages, 4591 KiB

Open AccessReview

Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

by Pascal Roland Enok Bonong, Monica Zahreddine, Chantal Buteau, Michel Duval, Louise Laporte, Jacques Lacroix, Caroline Alfieri and Helen Trottier

Vaccines 2021, 9(3), 288; https://doi.org/10.3390/vaccines9030288 - 19 Mar 2021

Cited by 14 | Viewed by 3656

Abstract

This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92–9.45) and 4.17 (95% CI: 2.61–6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

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10 pages, 947 KiB

Open AccessBrief Report

Humoral Immunity to Varicella Zoster Virus in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis Compared to Healthy Controls

by Marco Krasselt, Christoph Baerwald, Uwe G. Liebert and Olga Seifert

Vaccines 2021, 9(4), 325; https://doi.org/10.3390/vaccines9040325 - 1 Apr 2021

Cited by 9 | Viewed by 2785

Abstract

Background: The prevalence of herpes zoster (HZ) is high in patients with rheumatic diseases. Systemic lupus erythematosus (SLE) doubles the risk for developing HZ. However, little is known about natural humoral immunity against varicella zoster virus (VZV) in patients with SLE. Hence, we compared VZV IgG antibody concentrations in a group of SLE patients with healthy controls and patients with rheumatoid arthritis (RA). Methods: n = 56 patients with SLE, n = 54 patients with RA, and n = 56 healthy controls were included in this study. The VZV IgG antibody concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The antibody concentrations were compared between the groups. Results: Overall IgG antibody titers for VZV in SLE patients were comparable to healthy controls but higher when compared to patients with rheumatoid arthritis (p = 0.0012). In consequence, antibody levels in controls were higher than in RA patients (p = 0.0097). Stratification by age revealed highest titers among SLE patients in the fourth life decade (p = 0.03 for controls, p = 0.0008 for RA patients) whereas RA patients in their sixth decade had the lowest antibody concentration (p = 0.03 for controls, p = 0.04 for SLE patients). Regarding the individual HZ history, antibody levels of SLE patients with a positive history exceeded all other groups. Conclusions: Although humoral VZV immunity in SLE patients is comparable to healthy controls it seems to be pronounced in young SLE patients between 30 and 39. The lowest VZV IgG levels were found in RA patients. HZ seems to induce antibody production, particularly in patients with SLE. Immunological processes might contribute to VZV antibody levels in SLE patients, but further investigations are needed to substantiate this hypothesis. Even though the increased HZ prevalence seems to be independent of humoral immunity in SLE patients, reduced humoral immunity might contribute to HZ in RA patients. The available HZ subunit vaccination might be an appropriate way to reduce the HZ risk in patients with rheumatic diseases. Full article

(This article belongs to the Special Issue Herpesvirus-Specific Immunomonitoring in Patient Groups of Increased Risk)

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