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Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23–4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

BACKGROUND Seasonal influenza affects 5%-15% of Americans annually, resulting in preventable deaths and significant economic impact. Influenza infection is particularly dangerous for people with cardiovascular disease, who therefore represent a priority group for vaccination campaigns. OBJECTIVE We aimed to assess the effects of digital intervention messaging on self-reported rates of seasonal influenza vaccination. METHODS This was a randomized, controlled, single-blind decentralized trial conducted at individual locations throughout the United States over the 2020-2021 influenza season. Adults with self-reported cardiovascular disease who were members of the mobile Achievement platform were randomized to receive or not receive a series of 6 patient-centered digital intervention messages promoting influenza vaccination. The primary endpoint was the between-group difference in self-reported vaccination rates at 6 months after randomization. Secondary outcomes included levels of engagement with messages and the relationship between vaccination rates and engagement with messages. Subgroup analyses examined variation in intervention effects by race. Controlling for randomization group, we examined the impact of other predictors of vaccination status, including cardiovascular condition type, vaccine drivers/barriers, and vaccine knowledge. RESULTS Of the 49,138 randomized participants, responses on the primary endpoint were available for 11,237 (23%; 5575 in the intervention group and 5662 in the control group). The vaccination rate was significantly higher in the intervention group than among controls: 3418/5575 (61.31%) vs. 3355/5662 (59.25%), respectively; relative risk 1.03 [95% CI 1.004-1.066]; P=.027). Participants who were older, more educated, and White or Asian were more likely to report being vaccinated. The intervention was effective among White participants (P=.004) but not among people of color (P=.422). The vaccination rate was 15 percentage points higher among participants who completed all 6 intervention messages versus none, and at least 2 completed messages appeared to be needed for effectiveness. Participants who reported a diagnosis of COVID-19 were more likely to be vaccinated for influenza regardless of treatment assignment. CONCLUSIONS This personalized, evidence-based digital intervention was effective in increasing vaccination rates in this population of high-risk people with cardiovascular disease. CLINICALTRIAL ClinicalTrials.gov NCT04584645; https://clinicaltrials.gov/ct2/show/NCT04584645

Solid organ transplantation is an effective treatment for patients with end-stage organ disease. The prevalence of cardiovascular diseases (CVD) has increased in recipients. CVD remains a leading cause of mortality among recipients with functioning grafts. The pathophysiology of CVD recipients is a complex interplay between preexisting risk factors, metabolic sequelae of immunosuppressive agents, infection, and rejection. Risk modification must be weighed against the risk of mortality owing to rejection or infection. Aggressive risk stratification and modification before and after transplantation and tailoring immunosuppressive regimens are essential to prevent complications and improve short-term and long-term mortality and graft survival.

Aim The “holy grail” of transplantation is donor specific tolerance in the absence of immunosuppression. There are no cases reported of survival without immunosuppression in heart transplant recipients. This prospective study identifies a group of heart transplant recipients who have developed tolerance to the transplanted organ. We hypothesize that these recipients were pre-disposed to survival without immunosuppression. Identification of a gene signature in these recipients could help understand the mechanism of development of transplant tolerance in heart transplant recipients. Methods We identified 8 cardiac transplant patients with a history of at least 7 days without immunosuppression (TOL group). Comparator groups included (i) 120 days post-transplant patients without rejection (11 pts), (ii) 5 years post-transplant patients with normal graft function (15 pts) (iii) patients with acute cellular rejection ISHLT 2R or greater (5 pts). Blood samples were obtained and total RNA extracted from PBMCs was reverse transcribed to cDNA. The cDNA was overlaid onto 96-well PCR plates containing customized gene-specific PCR primer pairs for Treg regulation genes and analyzed using quantitative Real Time PCR. Results We observed 15 genes which were differentially expressed between the TOL and rejector (REJX) groups. As shown in Table 1, genes that play an important role in the regulation of Tregs that is central to the development of a potentially tolerant state showed a significant higher expression in the TOL group as compared to REJX group. Conclusions This is the first report of a group of heart transplant patients surviving more than transiently without immunosuppression. The existence of these patients and the documented gene expression differences supports further research into mechanisms and potential ways to identify the development of tolerance in heart transplant patients. Download : Download high-res image (89KB) Download : Download full-size image