The threshold of 6
The threshold of 6.2 log cp/mL is associated with a negative predictive value of 93.5% (in case of high TTV viral load) and a positive predictive value of 47.9% (in case of low TTV viral load) for vaccine response in this cohort. Nonresponse was associated with TTV VL 6.2 log10copies/mL before vaccination (Odds Ratio (OR) = 17.87, 95% confidence interval (CI95) = 3.02-105.72), mycophenolate treatment (OR = 4.73, CI95 = 1.46-15.34) and BNT162b2 (n = 34; vs mRNA-1273, n = 101) vaccine (OR = 6.72, CI95 = 1.75-25.92). In second dose non-responders, TTV VL 6.2 or <3.2 log10copies/mL before the third dose was associated with low (0/19) and high (9/10) rates of seroconversion. == CONCLUSION == COVID-19-naive LTR respond poorly to three doses of mRNA vaccine, Clobetasol especially those with high TTV VL. Future studies could further evaluate this biomarker as a guide for vaccine strategies. Keywords:lung transplantation, COVID-19 vaccine, Torque teno virus, vaccine response, immunosuppression Abbreviations:BAU, Binding Antibody Unit; ED50, half-maximal effective dilution; MMF/MPA, mycophenolate mofetil/mycophenolic acid; TTV, Torque teno virus == Introduction == Lung transplant recipients (LTR) are at high risk for severe COVID-19 due to their lung disease and the Rabbit polyclonal to ZNF165 high doses of immunosuppressive drug therapy they receive to prevent allograft rejection.1,2The highly transmissible omicron variant is resistant to several anti-SARS-CoV-2 monoclonal antibodies, and still represents a major issue in this population. Moreover, the combination of protease inhibitors nirmatrelvir/ritonavir (Paxlovid) is difficult to use in this population due to significant drug interactions. In this context, the COVID vaccine remains the safest strategy to protect LTR from severe disease. By the end of 2020, solid organ transplant recipients were prioritized for COVID-19 mRNA vaccination. However, they have been shown to only develop a poor antibody response (34%-54%) to a 2-dose vaccine regimen compared to immunocompetent individuals,3,4with lower response observed in LTR (0-40%) than in Clobetasol kidney or liver transplant recipients since they receive higher doses of immunosuppressive drugs.5,6,7,8,9,10,11Previous studies showed that around half of solid organ recipients who were nonresponders to the second dose seroconverted after a third mRNA vaccine dose, given as booster.12,13,14,15However, only few studies have determined the effectiveness of a third vaccine dose in LTR,16,17and markers predictive of vaccine response are still lacking. In order to quantify the impact of immunosuppression Clobetasol on vaccine response and hopefully to predict response or nonresponse, one should be able to quantify the level of immunosuppression. Previous studies have reported that the composition of the virome in plasma is affected by immunosuppressant drugs and may therefore predict the state of immunosuppression.18In transplant recipients, the virome is mostly composed ofAnelloviridae(68%) andHerpesviridae(13%).18Torque teno virus (TTV) accounts for 97% ofAnelloviridaefraction in the virome,18and viral DNA loads (VL) in healthy individuals typically remain below 4 log10cp/mL.19In the case of immunosuppression, this virus replicates strongly, and the level of its burden has made it possible to stratify rejecting and non-rejecting recipients.18This makes it a potential candidate for predicting vaccine response in transplant recipients. Among theHerpesviridae, increased VL of Epstein-Barr virus and Cytomegalovirus may also reflect immunosuppression status. However, antivirals used for prophylaxis after transplantation significantly decrease the load of these viruses and may prevent their use as effective markers of immunosuppression. In this study, we characterized the antibody response in LTR after three doses of mRNA vaccine, by longitudinally analyzing anti-Receptor Binding Domain (RBD) IgG titers and neutralizing activity of sera against the ancestral strain D614G, B.1.617.2 (delta), and B.1.1.529 (omicron) variants. In posthoc analyses, we used logistic regression to assess for an association of demographic, clinical, and TTV VL variables with vaccine Clobetasol response. == Methods == == Study design == We conducted Clobetasol a.