Alternative strategies to increase immunogenicity of COVID-19 vaccines in immunosuppressed kidney transplant recipients are evaluated in clinical trial.
Repeating a booster dose increased the immune response to COVID-19 vaccine in kidney transplant recipients as well or better than repeating the primary 2-dose regimen or interrupting their immunosuppressant with the booster in a trial that investigators report is the first to compare alternative strategies to improving vaccine response in this population.
"...even after a third or fourth vaccination, a considerable proportion of organ transplant recipients remains a serological non-responder. It is therefore imperative to investigate whether alternative vaccination strategies could be more immunogenic," explained Luuk Hilbrands, PhD, Department of Nephrology, University of Amsterdam, Amsterdam, Netherlands, and colleagues.
The investigators enrolled study participants from among kidney transplant recipients (KTR) in the Netherlands who did not have serologic response 14-56 days after a 2-dose primary vaccination or 3rd-dose booster with the mRNA-1273 (Moderna) vaccine. Serologic response was measured by anti-SARS-CoV-2 RBD IgG ELISA assay, with cutoff level for seropositivity of ≥50 binding antibodies units (BAU)/ml.
Participants were randomized to receive either another 2-dose vaccination with mRNA-1273 (n=77); a different vaccine, Ad26.COV2.S (Janssen) (n=78); or to a control group receiving a single booster dose of mRNA-1273 (n=75). In addition, two groups receiving the booster dose either maintained their mycophenolate mofetil- mycophenolic acid (MMF-MFA) (n=53) or discontinued it 1 week before through 1 week after the vaccination (n=52).
Hilbrands and colleagues had noted a strong negative association between MMF-MFA and vaccine immunogenicity, and so sought to determine whether discontinuation might improve immune response. All those who agreed to be randomized to maintain or discontinue MMF-MFA were receiving triple immuosuppressive therapy consisting of a calcineurin inhibitor, MMF or MFA, and steroids.
"Reduction of immunosuppression in patients using dual therapy was not deemed feasible," Hilbrands commented to Contagion.
"Another (untested) strategy could be to replace MMF by another immunosuppressant, (such as) azathioprine or an mTOR inhibitor," he opined.
An additional condition that is yet to be tested is withholding of MMF-MFA at the time of the full, 2 dose primary vaccination."The reason to withhold MMF during 2 weeks (in the trial) is the observation that in the basic vaccination schedule, patients using MMF were low responders. So, at the time of basic vaccination schedule, this information was not available," Hilbrands pointed out.
The investigators reported that vaccination with the 2-dose mRNA-1273 or Ad26.COV2-S were not superior to single dose mRNA-1273; with seroresponse rates of 68%, 63% and 68%, respectively. The holding of MMF-MFA was also not statistically significantly superior to maintaining the immunosuppressant; with seroresponse rates of 80% and 67%, respectively.
Hilbrands and colleagues concluded that repeated vaccination increases SARS-CoV-2-specific antibodies in KTRs without additional effect fromhigher doses, a heterologous vaccine, or 2 weeks discontinuation of MMF-MFA. They cite other studies demonstrating increased seroresponsive rates after each additional booster vaccination; and advise repeating booster vaccination to achieve stronger response.
"We think that our results are directly useful for doctors caring not only for kidney transplant recipients, but also for other patients on immunosuppresive drugs," they indicate.