Antibody and T-Cell Responses 6 Months After Coronavirus Disease 2019 Messenger RNA-1273 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant

Abstract

Background: The immune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTRs) and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls.

Methods: A total of 152 participants with CKD stages G4/5 (eGFR <30 mL/min/1.73 m2), 145 participants on dialysis, 267 KTRs, and 181 controls were included. SARS-CoV-2 Spike S1 specific IgG antibodies were measured using fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta, and Omicron (BA.1) variants by plaque reduction, and T-cell responses by interferon-γ release assay.

Results: At 6 months after vaccination, S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTRs. These figures were comparable to the response rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variants was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected at 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTRs. T-cell responses at 6 months were significantly lower than responses at 28 days.

Conclusions: Although seropositivity rates at 6 months were comparable to rates at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTRs.

Clinical trials registration: NCT04741386.

Keywords: COVID-19; chronic kidney disease; dialysis; kidney transplantation; mRNA-1273 vaccine.

Figure 1.

Participant enrollment and outcomes 6 months after second vaccination. Abbreviations: CKD G4/5, chronic kidney disease stages 4/5; COVID-19, coronavirus disease 2019.

Figure 2.

Seroconversion rate (A) and S1-specific IgG antibody levels (B) at day 28 and month 6 after second coronavirus disease 2019 vaccination per cohort. Depicted are scatter dot plots with a line indicating the median level. P values were calculated using the Wilcoxon signed rank test. Abbreviations: BAU/mL, binding antibody units per milliliter; CKD G4/5, chronic kidney disease stages 4/5; IgG, immunoglobulin G; KTR, kidney transplant recipient.

Figure 3.

Decay in antibodies according to exponential decay model. A, Decay per group in participants with antibody value at day 28 ≥10 BAU/mL. B, Estimated time until 10 BAU/mL. Abbreviations: BAU/mL, binding antibody units per milliliter; CKD G4/5, chronic kidney disease stages 4/5; IgG, immunoglobulin G; KTR, kidney transplant recipient.

Figure 4.

Levels of neutralizing antibodies against the ancestral SARS-CoV-2 (wild type) and the recently emerged Delta and Omicron variants per subgroup and compared with level of neutralizing antibodies at 6 months. The dotted horizontal line indicates the lower limit of detection of neutralization (titer of 20). P values were calculated using the Wilcoxon signed rank test. Abbreviations: CKD G4/5, chronic kidney disease stages 4/5; KTR, kidney transplant recipient; LLoD, lower limit of dectection; PRNT50, 50% plaque reduction neutralization test.

Figure 5.

SARS-CoV-2–specific T-cell response in all participants at 1 of the participating centers. A, Percentage of T-cell responders per group 6 months after vaccination (defined as Antigen-2 ≥0.15 IU/mL). B, Individual IFN-γ levels per group, with the horizontal line representing the median value. Dotted horizontal line indicates the threshold of detectable T-cell response (≥0.15 IU/mL). P values were calculated using the Wilcoxon signed rank test. Abbreviations: CKD G4/5, chronic kidney disease stages 4/5; IFN-γ, interferon gamma; KTR, kidney transplant recipient.