Impact of immunosuppressive treatment and type of SARS-CoV-2 vaccine on antibody levels after three vaccinations in patients with chronic kidney disease or kidney replacement therapy

Abstract

Background Patients with chronic kidney disease or kidney replacement therapy demonstrate lower antibody levels after SARS-CoV-2 vaccination compared to healthy controls. In a prospective cohort, we analysed the impact of immunosuppressive treatment and type of vaccine on antibody levels after three SARS-CoV-2 vaccinations. Methods Control subjects (n = 186), patients with CKD G4/5 (n = 400), dialysis patients (n = 480) and kidney transplant recipients (KTR) (n = 2468) were vaccinated with either mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford/AstraZeneca) in the Dutch SARS-CoV-2 vaccination programme. Third vaccination data were available in a subgroup of patients (n = 1829). Blood samples and questionnaires were obtained one month after the second and third vaccination. Primary endpoint was the antibody level in relation to immunosuppressive treatment and type of vaccine. Secondary endpoint was occurrence of adverse events after vaccination. Results Antibody levels after two and three vaccinations were lower in patients with CKD G4/5 and dialysis patients with immunosuppressive treatment compared to patients without immunosuppressive treatment. After two vaccinations, we observed lower antibody levels in KTR using mycophenolate mofetil (MMF) compared to KTR not using MMF (20 BAU/ml [3–113] versus 340 BAU/ml [50–1492], P < 0.001). Seroconversion was observed in 35% of KTR using MMF, compared to 75% of KTR not using MMF. Of the KTR who used MMF and did not seroconvert, eventually 45% seroconverted after a third vaccination. mRNA-1273 induces higher antibody levels as well as a higher frequency of adverse events compared to BNT162b2 in all patient groups. Conclusions Immunosuppressive treatment adversely affects the antibody levels after SARS-CoV-2 vaccination in patients with CKD G4/5, dialysis patients and KTR. mRNA-1273 vaccine induces a higher antibody level and higher frequency of adverse events.

A Third Dose of SARS-CoV-2 mRNA Vaccine Improves Immune Response in Chronic Kidney Disease Patients

“…Similar to other reports with ChAdOx1 and mRNA vaccines [ 44 , 50 ], we observed that even after a third dose of BNT162b2 a proportion of KT patients do not have neutralizing antibodies, especially patients under mycophenolic acid or sodium mycophenolate treatments, consistent with previous reports showing decreased humoral responses in patients receiving mycophenolate [ 33 , 34 , 51 ]. It has been shown that mycophenolic acid significantly inhibits proliferation and differentiation of primary human B cells, impairing immunoglobulin secretion of activated but not terminally differentiated B cells [ 52 ].…”

Hybrid immunity improves the immune response after fourth Covid-19 vaccine dose in individuals with medical conditions predisposing to severe Covid-19

“…The third vaccine dose given more than three months after the primary vaccination has been shown in patients with RD to increase the RBD-IgG level, NAb titer against wt/Omicron and T cell response significantly, and compared to healthy controls lower or similar response levels have been reported [37, 39]. In patients with CKD, the third dose has been demonstrated to increase the antibody levels, proportion of participants with NAbs and NAb titer levels and T cell responses [40–43] and seroconversion has been observed in patients who did not respond after two vaccine doses [34, 44]. However, in kidney transplant recipients the rates of response have remained suboptimal [41].…”

“…We determined the lower limit of a normal antibody response to vaccination as the 5 th percentile of the antibody concentrations; 398 and 716 BAU/ml for RBD-IgG and SFL-IgG, respectively. All controls had NAb against WT and Omicron BA.1; with GMTs 404 (95% CI 269-608) and 26 (95% CI [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35], respectively (Figure 3).…”

Hybrid Immunity Improves the Immune Response after the Fourth COVID-19 Vaccine Dose in Individuals with Medical Conditions Predisposing to Severe COVID-19

“…CKD and RD associated with immunosuppressive therapy have also, in previous studies, shown to impact immune responses to COVID-19 vaccinations. Previous studies have shown overall seroconversion rates being as high as in healthy controls after the primary vaccination [ 34 , 35 , 36 ] but with significantly lower mean RBD-IgG antibody levels, NAb antibody titers (against wt), and lower T-cell responses compared to healthy subjects [ 6 , 34 , 37 , 38 , 39 ]. The third vaccine dose given more than three months after the primary vaccination has been shown in patients with RD to increase the RBD-IgG level, NAb titer against wt/Omicron and T cell response significantly, and compared to healthy controls lower or similar response levels have been reported [ 38 , 40 ].…”