The mean age of transplant recipients has significantly increased the last decennia and older patients are facing higher risk for infectious complications. Varicella zoster virus (VZV) can establish a lifelong latency in the dorsal root ganglia after primary infection and reactivation of VZV leads to herpes zoster (HZ). The risk factors for developing HZ include advancing age and weakening of the immune system. We investigated the ageing of the immune system in kidney and lung transplant patients and we found a significant shift from naive to memory T cells after transplantation, especially in older patients. Cytomegalovirus latency drove the lower expression of CD28 (seen as immunosenescence) in transplant patients more than the age at transplantation. Besides, we found VZV-specific cellular immunity did not markedly change following kidney transplantation and this suggests the potential benefit of preventive vaccination before transplantation. Therefore, we vaccinated patients waiting for lung transplantation with a live-attenuated HZ vaccine and the results showed that this vaccine was safe and induced a robust immune response in lung transplant candidates. By measuring the frequencies of T and B cell subsets in vaccinated patients, we concluded that increased levels of age associated B cells might disturb the cellular immune response to HZ vaccination. Lastly, we established an in vitro model which could be used to study molecular mechanisms of reactivation of the latent VZV in the future.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2021|