Herpes Virus Infections in Kidney Transplant Patients : Investigation of Kidney Transplant Patients for Antibodies and T-cells After Herpes Virus Vaccination and Infection

Kidney transplantation is a life-saving procedure for patients with kidney failure, and in 2021, 252 kidney transplantations were performed in Denmark. Varicella-zoster virus (VZV) is a vaccine-preventable disease that causes varicella during primary infection and herpes zoster when reactivated later in life. VZV is one of the most common infections after organ transplantation, and kidney transplant recipients have high risk of herpes zoster (annual incidence: 3 per 100). Furthermore, kidney transplant recipients that acquire herpes zoster have high risk of disseminated and severe disease as well as increased risk of post-herpetic neuralgia.Until 2021, the only available VZV/herpes zoster vaccines in Europe were live vaccines, and live vaccines are contraindicated in immunosuppressed individuals due to the risk of infection with the vaccine strain. However, a new, non-live, recombinant subunit herpes zoster vaccine (Shingrix®) that can be used in immunosuppressed individuals was recently approved and became available in Denmark in October 2021.The efficacy of Shingrix® in healthy individuals is excellent (90%) both with regard to preventing herpes zoster and post-herpetic neuralgia. However, organ transplant recipients receive high doses of immunosuppressive medication, and information on efficacy and immunogenicity of Shingrix® in immunosuppressed individuals is sparse. One randomized study found the efficacy of the vaccine to be good (68%) in patients after hematopoietic stem cell transplantation. Furthermore, one phase III randomized, placebo-controlled study was conducted in 246 kidney transplant recipients, and the vaccine was found to be safe and to induce antibody responses, but the study was not powered to demonstrate efficacy.At present, international guidelines recommend vaccination against herpes zoster prior to or after transplantation, but there is no information about the optimal timing of vaccination or duration of the immune response in transplant recipients.Poor or no antibody response after vaccinations are documented among organ transplant recipients. Vaccination prior to transplantation or early post-transplantation may be of benefit because patients are at the highest risk of infections early post-transplantation due to high load of immunosuppressive therapy, however, this is also the period with the highest risk of non-response to vaccines. It is therefore of great importance, for both individual patients and for society, to determine the optimal timing of vaccination, response rates and duration of protection prior to use of vaccines in organ transplant recipients.The investigators will conduct a prospective observational exploratory study including kidney transplant candidates and recipients who are offered Shingrix® vaccination. Shingrix® vaccination is routine care, and vaccination is not a part of the study, and acceptance of vaccination is not mandatory to participate in the study. The study is a national collaboration that includes all Danish kidney transplantation centers and kidney transplant recipients from all Danish regions. The study has potential to contribute with necessary information to design optimal programs for vaccine roll-out and thereby to reduce the incidence of herpes zoster and herpes zoster-related complications including hospital admissions in kidney transplant recipients as well as other solid organ transplant recipients. Furthermore, the investigators will explore differences in the immune systems of kidney transplant recipients who get VZV infections and those who don't.The study aims to include 875 patients, of which 500 will be kidney transplant recipients (250 who are 6-12 months post-transplantation, 125 who are 12-18 months post-transplantation and 125 who are >24 months post-transplantation) and 375 kidney transplant candidates from the kidney transplant waitlist.For participants on the transplant waitlist, blood will be collected at inclusion and 1, 2, 6 and 12 months post-inclusion, as well as 6 and 12 months post-transplantation and in the case of VZV infection. For participants who are already transplanted at inclusion, blood will be collected at inclusion, and 1, 2, 6 and 12 months post-inclusion and in the case of VZV infection. Plasma and peripheral blood mononuclear cells (PBMC) will be stored in a biobank.All participants will be asked at inclusion to fill out a questionnaire regarding health, lifestyle, and vaccine history. At follow-ups, participants will be asked to fill out a questionnaire regarding changes in VZV infection history, vaccination history, transplant related factors and medication. Furthermore, health data will be collected from hospital records and national registries. Measurement of VZV glycoprotein E antibodies will be done using enzyme-linked immunosorbent assays (ELISA). Identification and phenotyping of VZV-specific T cells will be done through DNA-barcode labelling and flow cytometry. Cytokine profiling will be done using a Luminex MILLIPLEX assay. Analyses will be performed at the Technical University of Denmark..

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 10. Apr. Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Chickenpox Communicable Diseases Herpes Zoster Infections Recruitment Status: Recruiting Study Type: Observational Vaccine-Preventable Diseases Varicella Zoster Virus Infection Virus Diseases

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: November 3, 2022, Last downloaded: ClinicalTrials.gov processed this data on April 17, 2024, Last updated: April 17, 2024

Study ID:	NCT05604911 H-22042603 0073947
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PPN (Katalog-ID):	CTG008761175