High incidence and viral load of HHV-6A in a multi-centre kidney transplant cohort

Human herpesvirus 6 (HHV-6) is a common opportunistic pathogen in kidney transplant recipients. Two distinct species of HHV-6, HHV-6A and HHV-6B, have been identified, of which the latter seems to be dominant. However, it is unclear whether they increase the likelihood of other viral reactivations. We characterized a multi-centre cohort of 93 patients along nine study visits for viral load. We tested for the following viruses: HHV-6A and HHV-6B, the herpesviruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV) and the polyomavirus BK (BKV). We detected HHV-6A viral load in 48 (51.6%) patients, while the incidence of HHV-6B was much lower, being detected in 6 (6.5%) patients. The incidence of HHV-6A was higher than of BKV, CMV and EBV. HHV-6A also demonstrated higher viral loads than the rest of viruses. There was a non-significant trend of association between HHV-6A and HHV-6B as co-infection, whereas no increased incidence of other viruses among patients with HHV-6A reactivation was observed. There was no negative effect of high HHV-6A (>10,000 copies/ml) load on markers of renal graft and hepatic function or blood count twelve months post-transplant. In contrast to previously published data, our results show a clear dominance of HHV-6A in peripheral blood when compared to HHV-6B, with higher incidence and viral load levels. Despite the high HHV-6A loads observed, we did not identify any negative effects on posttransplant outcome

The role of pre-existing cross-reactive central memory CD4 T-cells in vaccination with previously unseen influenza strains.

Influenza vaccination is a common approach to prevent seasonal and pandemic influenza. Pre-existing antibodies against close viral strains might impair antibody formation against previously unseen strains-a process called original antigenic sin. The role of this pre-existing cellular immunity in this process is, despite some hints from animal models, not clear. Here, we analyzed cellular and humoral immunity in healthy individuals before and after vaccination with seasonal influenza vaccine. Based on influenza-specific hemagglutination inhibiting (HI) titers, vaccinees were grouped into HI-negative and -positive cohorts followed by in-depth cytometric and TCR repertoire analysis. Both serological groups revealed cross-reactive T-cell memory to the vaccine strains at baseline that gave rise to the majority of vaccine-specific T-cells post vaccination. On the contrary, very limited number of vaccine-specific T-cell clones was recruited from the naive pool. Furthermore, baseline quantity of vaccine-specific central memory helper T-cells and clonotype richness of this population directly correlated with the vaccination efficacy. Our findings suggest that the deliberate recruitment of pre-existing cross-reactive cellular memory might help to improve vaccination outcome