Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine Booster Doses in Kidney Transplant Recipients: Results of a 12-mo Follow-up From a Prospective Observational Study

Abstract

Background: Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs.

Methods: A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology.

Results: Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [e^β] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (e^β 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (e^β1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19.

Conclusions: Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725).

FIGURE 1.

Study flowchart. Five hundred fifty-nine KTRs were considered for inclusion, 415 did not consent to participate, and 144 were enrolled in the study. One hundred twenty-three KTRs were included in the final analysis, because 21 enrolled KTRs attended only the D0 visit. Furthermore, 1 participant experienced graft loss between 3 and 6 mo visit, and 1 participant experienced graft loss, and 3 participants died between 6 and 12 mo visit. KTR, kidney transplant recipient.

FIGURE 2.

Anti–SARS-CoV-2 IgG levels development in all 4 time points. The y-axis shows IgG antibody levels, log transformed. X-axes show time points: D0: baseline, M3: 3 mo, M6: 6 mo, and M12: 12 mo—(A) all data, (B) antibody levels based on sex, (C) antibody levels in 2 groups: older than median and younger than median age, and (D) antibody levels after exclusion of KTRs who were either administered fourth dose during the follow-up or were infected with SARSCoV-2. The statistical significance was computed using the paired Wilcoxon test. KTR, kidney transplant recipient.

FIGURE 3.

Dynamics of anti-HLA antibody in all 4 time points. X-axes show time points: D0: baseline, M3: 3 mo, M6: 6 mo, and M12: 12 mo. The P values show the 1-sided Wilcoxon test comparing baseline and 1 of 3 time points. The statistical tests are in Table S3 (SDC, http://links.lww.com/TXD/A655)—(A) peak MFI, (B) mean MFI, (C) MFI of immunodominant anti-HLA antibody at baseline, (D) median MFI of all positive antibodies, (E) counts of positive anti-HLA antibodies, and (F) cPRAs. cPRA, calculated panel-reactive antibody; MFI, mean fluorescence intensity.

FIGURE 4.

Anti-HLA antibody development in COVID-19-infected subgroup (n = 27) and subgroup administered fourth dose during follow-up (n = 32). The P values show the 1-sided Wilcoxon test comparing before and after events (COVID-19 or fourth dose)—(A) maximum MFI before and after COVID-19 infection, (B) mean MFI before and after COVID-19 infection, (C) maximum MFI before and after fourth dose, (D) mean MFI before and after fourth dose. MFI, mean fluorescence intensity.