A Randomized, Controlled, Double-Blind Trial of Inulin to Boost Response to a Third COVID-19 Vaccine Dose in Kidney Transplant Recipients

ABSTRACT

Purpose: Kidney transplant recipients (KTR) commonly exhibit inadequate responses to 2-dose COVID-19 vaccination schedules and remain at increased risk of severe COVID-19. Gut dysbiosis is common among KTRs and has been associated with poor vaccine responses. We hypothesised that a dietary fibre supplement may correct dysbiosis and enhance responses to a third dose of COVID-19 vaccine in KTRs. Method(s) KTRs who had received 2 doses of a COVID-19 vaccine were recruited from 2 transplant programs in Australia. KTRs with an inadequate response (defined by anti-RBD <100U/mL) were randomised to receive inulin (fibre) or maltodextran (control), 10g dissolved in 200ml water twice daily for 4 weeks prior to, and 4 weeks after a 3rd vaccine, at which time vaccine response was measured by anti-RBD titre, vaccine-specific B and T cell responses, and changes in the gut microbiome. Patients and investigators were blinded to treatment assignment. COVID-19 infection was excluded by measurement of anti-nucleocapsid antigen. Result(s) Of 85 KTRs screened, 71 had baseline anti-RBD<100U/mL and were randomised to inulin (n=37) or control (n=34). Participants were 33% female, mean age 59 yrs (SD 11), with mean eGFR 56 ml/min/1.73m2 (SD 24.8), and were most commonly receiving tacrolimus, mycophenolate and prednisolone. All participants received a third dose of a mRNA COVID-19 vaccine after receiving a dietary supplement for 4 weeks. Week 8 assessment of vaccine response, supplement tolerability and change in microbiome are ongoing. Four participants tested positive for COVID-19 during the study. Conclusion(s) Gut dysbiosis is one potential contributor to the poor COVID-19 vaccine responses exhibited by KTRs. This trial will determine whether a simple dietary fibre supplement is well tolerated and effective in correcting gut dysbiosis and restoring vaccine responsiveness. Improved vaccine responses are urgently required to better protect KTRs from ongoing morbidity and mortality from COVID-19.