Repeated COVID-19 Booster Vaccination Needed for Kidney Transplant Recipients

Repeated COVID-19 vaccination achieves stronger immune responses in kidney transplant recipients, but higher doses or heterologous vaccination provide no further benefit.

Results of a study published in The Lancet Infectious Diseases found little evidence supporting particular SARS-CoV-2 vaccine types or immunosuppressant discontinuation strategies to improve immune responses among kidney transplant recipients.

Researchers conducted a prospective, open-label, randomized controlled trial at 4 sites in the Netherlands between October 2021 and February 2022. Adult kidney transplant recipients were randomly assigned in a 1:1:1 fashion to receive either 1 (n=73) or 2 (n=72) doses of the mRNA-1273 vaccine or 1 dose of the Ad26.COV2-S (n=73) vaccine. A second group of patients who were receiving triple immunosuppressive therapy with calcineurin inhibitor, mycophenolate mofetil or mycophenolic acid, and steroids were randomly assigned in a 1:1 fashion to either continue (n=46) or discontinue (n=46) mycophenolate mofetil acid treatment 1 week prior to receiving 1 mRNA-1273 vaccine dose. The primary outcomes were seroconversion and SARS-CoV-2 spike protein (S1)-specific immunoglobulin G concentration at 28 days after vaccination.

Among patients included in the analysis, the mean age ranged from 57.3 to 60.5 years, 34% to 52% were women, and 76% to 88% had received 1 kidney transplant. In addition, patients were receiving a median of 2 to 3 immunosuppressive agents, 67% to 100% had received 2 prior COVID-19 vaccine doses, and 15% to 30% were seropositive at baseline.

Repeated vaccinations are the most successful strategy to achieve a humoral immune response in kidney transplant recipients.

Compared with patients in the first group who received  single-dose COVID-19 mRNA vaccination, seropositivity rates at day 28 did not significantly differ among the 2-dose recipients (-0.4%; P =.96) or the Ad26.COV2-S recipients (-6%; P =.49). There also were no significant differences in median S1-specific antibody concentrations observed at day 28 among single-dose mRNA vaccine recipients (156 binding antibody units [BAU]/mL) compared with 2-dose recipients (92.2 BAU/mL; P =.94) and Ad26.COV2-S recipients (74.7 BAU/mL; P =.10).

Compared with patients in the second group who continued mycophenolate mofetil acid, those who discontinued treatment did not significantly differ in regard to seropositivity rates at day 28 (range, 67%-80%; P =.15). Median S1-specific antibody concentrations at day 28 also did not significantly differ between these patients (143 vs 119 BAU/mL, respectively; P =.29).

In a random sample of 25 patients from each of the 5 groups, neutralizing activities were evaluated for the Delta and Omicron variants. No significant trends were observed.

Adverse events were reported by 94% to 96% of patients who received the single-dose mRNA vaccine, 99% of those who received the 2-dose mRNA vaccine, and 79% of those who received the Ad26.COV2-S vaccine. Compared with single-dose COVID-19 mRNA vaccination, single-dose Ad26.COV2-S vaccination was associated with an overall decreased adverse event occurrence (P =.0024), with fewer injection site pain, local symptoms, and headache (all P £.034) events.

Study limitations include the short follow-up duration and the inability to achieve the targeted sample size.

Based on these findings, “Repeated vaccinations are the most successful strategy to achieve a humoral immune response in kidney transplant recipients,” the researchers concluded.

References:

Kho MML, Messchendorp AL, Frölke SC, et al. Alternative strategies to increase the immunogenicity of COVID-19 vaccines in kidney transplant recipients not responding to two or three doses of an mRNA vaccine (RECOVAC): a randomised clinical trial. Lancet Infect Dis. Published online October 27, 2022. doi:10.1016/S1473-3099(22)00650-8