Responses of Kidney Transplant Recipients to Vaccination and Boosting

Abstract

Objective: To assess heterologous booster (HB) with Janssen Ad26.COV2.S in kidney transplant recipients (KTRs) with low antibody levels after multiple COVID-19 mRNA vaccinations.

Patients and methods: This multicenter study examined anti-spike protein antibody levels in KTRs with two or more doses of mRNA vaccinations. Enrollment was from April 11, 2022, to September 19, 2023. Kidney transplant recipients with low levels (LL, 0.4-250 IU/mL) were offered HB with Janssen Ad26.COV2.S vaccine. Those with undetectable levels (UL, <0.4 IU/mL) were randomized to HB with or without immunosuppression adjustment. The primary endpoint was anti-spike protein antibody levels greater than 250 IU/mL (high level [HL]) at 28 days after HB. Subset analysis included lymphocyte, immunoglobulin, and COVID-19-specific T- and B-cell levels.

Results: Of the 419 unique KTRs assessed, 80.0% (n=335) were HL, 12.9% (n=54) were LL, and 7.2% (n=30) were UL. All KTRs vaccinated pretransplantation had detectable levels. Twenty-eight days after HB, 62.9% (n=22 of 35) of patients with LL achieved HL. Although 9 of 20 (45%) patients with UL achieved LL, none achieved HL by 28 days despite mycophenolate mofetil cessation before HB. Undetectable level was associated with fewer T and B cells in many subsets and fewer COVID-19-specific memory B cells.

Conclusion: Most KTRs had HL anti-spike protein antibodies after two or more mRNA vaccinations due to vaccinations with or without prior infection. Many LL patients responded to HB. No UL reached HL; likely due to severely impaired immune system. In this KTR population, a potential durable antibody response was identified if vaccinated before transplantation. Ultimately, monitoring antibody levels after vaccination might identify patients who could benefit from alternative prophylaxis strategies.

Clinicaltrials: gov NCT05220397.