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.
