Humoral Response After Five Successive Doses of SARS-CoV-2 mRNA Vaccine in Kidney Transplant Patients.

Abstract

The poor humoral response after vaccination against SARS-CoV-2 in kidney transplant (KT) patients led to the approval of successive booster doses.1 In recent weeks, the administration of a fifth dose of bivalent vaccines to KT, including components of the original virus strain and of the Omicron variant, was approved in Spain.2 The information about the effect of this new dose of messenger RNA (mRNA) vaccine on KT humoral response is limited and inaccurate.3,4 In our center, the humoral response to mRNA vaccine was prospectively studied in 16 stable KT recipients who received 5 successive doses between March 2021 and December 2022 (Table 1). They had not received monoclonal antibodies against the virus previously. No prior SARS-CoV-2 infection was confirmed by negative IgG antibodies against the nucleocapsid in all of them. The level of SARS-CoV-2 IgG anti-S antibodies at baseline and 1 mo after 2, 3, 4, and 5 doses was quantified by SARS-CoV-2 IgG chemiluminescent microparticle immunoassay (Abbott). Seroconversion was considered with an anti-S antibody titer greater than 260 BAU/mL. The seroconversion rate was 12.5% after 2 doses, 56.2% after the third, 81.2% after the fourth, and 93.8% after the fifth one. Only 1 KT did not develop antibodies after the fifth dose, who is the oldest in this series (73 y). Patients who seroconverted after 2 doses (n = 2) doubled the antibody titer after the third one; in those who seroconverted after 3 doses (n = 7), it increased by 380% after the fourth, and by 60% after the fifth one in those who seroconverted after 4 doses (n = 4). No patients presented acute rejection or serious adverse effects. TABLE 1. - Clinical and analytical characteristics of the patients N = 16 mRNA vaccine type, n (mRNA-1273/BNT162b2) 15/1 Male gender, n (%) 12 (75) Age, median [IQR] 61.5 [52.2–68] Diabetes, n (%) 9 (56.2) Time from KT to SARS-CoV-2 vaccine (mo), median [IQR] 50 [19.8–207] Serum creatinine at first dose, median [IQR] 1.3 [1–1.47] Induction immunosuppressive therapy, n (%) 9 (56.3) Tacrolimus, n (%) 15 (93.8) MPA, n (%) 11 (68.8) mTOR inhibitors, n (%) 3 (18.7) Prednisone, n (%) 16 (100) Thymoglobulin in the 2 y before SARS-CoV-2 vaccine, n (%) 5 (31.3) Rituximab in the year before SARS-CoV-2 vaccine, n (%) 0 Belatacept, n (%) 0 Non-heart-beating donor, n (%) 4 (25) Anti-S antibody titer after the second dose (BAU/mL), median 1070 Anti-S antibody titer after the third dose (BAU/mL), median [IQR] 1218 [689–2474] Anti-S antibody titer after the fourth dose (BAU/mL), median [IQR] 2029 [1021–5250] Anti-S antibody titer after the fifth dose (BAU/mL), median [IQR] 3105 [1466–5680] Time between KT and first dose (mo), median [IQR] 50 [19.7–207] Time between second and third doses (d), median [IQR] 127 [124.2–128.7] Time between third and fourth doses (d), median [IQR] 199 [196–204.7] Time between fourth and fifth doses (d), median [IQR] 202.5 [199.2–210] IQR, interquartile range; KT, kidney transplant; MPA, mycophenolic acid; mRNA, messenger RNA. An early experience in 8 KTs was reported with encouraging results, although not all received mRNA vaccines.3 Osmanodja et al retrospectively analyzed the serological response to the fifth dose in a cohort of KT patients.4 However, these patients had previously received different types of vaccines, not only mRNA, and mycophenolic acid dose adjustments was performed before the fourth dose, hindering the interpretation of their results. Our experience includes stable patients followed up prospectively without changes in their immunosuppressive therapy, which allows to analyze the effect of successive vaccine doses with fewer confounding factors. Our results support that successive doses progressively increase the seroconversion rate, allowing the majority of KT patients to maintain an adequate serological response. The limitations of our study include the small number of patients and the lack of information on cellular immunity. However, we present for the first time the evolution of the humoral response after 5 doses of mRNA vaccine in KT. In our opinion, it seems necessary to continue with the vaccination booster given the high seroconversion rate achieved. We must also identify those nonresponders who could benefit from passive immunization. However, the continuous mutations of the virus decrease the efficacy of monoclonal antibody-based prevention,5 so if the infection becomes endemic, it may be beneficial to continue with periodic vaccination boosters in KT patients, similar to the influenza vaccination strategies.