Weak antibody response to three doses of mRNA vaccine in kidney transplant recipients treated with belatacept

Abstract

Poor responses to mRNA COVID-19 vaccine have been reported after 2 vaccine injections in kidney transplant recipients (KTRs) treated with belatacept. We analyzed the humoral response in belatacept-treated KTRs without a history of SARS-CoV-2 infection who received three injections of BNT162b2-mRNA COVID-19 vaccine. We also investigated vaccine immunogenicity in belatacept-treated KTRs with prior COVID-19 and characterized symptomatic COVID-19 infections after the vaccine in belatacept-treated KTRs.Among the 62 belatacept-treated KTRs (36 [58%] males), the median age ( 63.5 years IQR [51-72]), without COVID-19 history, only four patients (6.4%) developed anti-SARS-CoV-2 IgG with low antibody titers (median 209, IQR [20-409] AU/ml). 71% were treated with mycophenolic acid and 100% with steroids in association with belatacept. In contrast, in all the 5 KTRs with prior COVID-19 history, mRNA vaccine induced a strong antibody response with high antibody titers (median 10 769 AU/ml, IQR [6410-20 069]) after two injections. Seroprevalence after three-vaccine doses in 35 non-belatacept-treated KTRs was 37.1%. Twelve KTRs developed symptomatic COVID-19 after vaccination, including severe forms (50% of mortality). Breakthrough COVID-19 occurred in 5% of fully vaccinated patients. Administration of a third dose of BNT162b2 mRNA COVID-19 vaccine did not improve immunogenicity in KTRs treated with belatacept without prior COVID-19. Other strategies aiming to improve patient protection are needed. K E Y W O R D S belatacept, COVID-19 mRNA vaccine, kidney transplant recipients, three doses 1 | INTRODUC TI ON In contrast to immunocompetent individuals, poor immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines have been observed in kidney transplant recipients (KTRs) after two vaccine injections. Several studies demonstrated seroconversion rates between 30% and 54% in patients treated with calcineurin inhibitors (CNI)-based immunosuppressive therapy. 1-5

Belatacept Use after Kidney Transplantation and Its Effects on Risk of Infection and COVID-19 Vaccine Response

“…In the same study, Chavarot et al [ 18 ] reported that the immune response to SARS-CoV-2 vaccination was better for patients with a history of COVID-19 infection before vaccination. Five KTx received two vaccine injections, including two patients that received three injections.…”

“…None had developed antibodies after the first or second dose. Two were treated with mycophenolic acid and the other two with azathioprine [ 18 ].…”

“…The second dose was performed 28 days after the first injection; the time between the second and third injection was 40 (36–69) days. In contrast to KTx, with no prior COVID-19 infection before vaccination, all patients developed a strong antibody response after vaccination [ 18 ].…”

“…Six (50%) patients died. Causes of death were an acute respiratory failure in four patients, myocardial infarction in one, and septic shock in one [ 18 ].…”

Observations on improving COVID-19 vaccination responses in kidney transplant recipients: heterologous vaccination and immunosuppression modulation

“…While poor humoral responses following 2 mRNA vaccine injections in KTRs treated with Belatacept has been well demonstrated 9 , 10 , 11 , whether a third dose could overcome these issues, as in patients receiving conventional therapy, remains controversial. Indeed, published rates of seroconversion varies dramatically from 6.4% (4 out of 62) in the study of Chavarot et al 12 , to 41% (5/12) in the report by Kamar et al 13 . These discrepancies could result from differences in confounding variables, especially the association with antiproliferative drugs, usually combined with Belatacept and recognized as risk factor for poor response to mRNA vaccines 14 .…”