Humoral Response of Renal Transplant Recipients to the BNT162b2 SARS-CoV-2 mRNA Vaccine Using Both RBD IgG and Neutralizing Antibodies

Abstract

Background. Data about SARS-CoV-2 vaccines efficacy in renal transplant recipients (RTR) are lacking. Methods. To reveal predictors for humoral response to BNT162b2 vaccine among RTR, patients were divided into positive (N = 42) and negative (N = 78) response groups based on receptor-binding domain (RBD) immunoglobulin G (IgG) ≥1.1 and neutralizing antibodies (NA) ≥16 dilution versus RBD IgG <1.1 or NA <16, respectively. NA were detected using a SARS-CoV-2 pseudo-virus. Results. NA were detected in only 42 of 120 (35%) of RTR versus 197 of 202 (97.5%) immunocompetent controls ( P < 0.001). NA geometric mean titers in RTR were significantly lower versus the control group {83.7 (95% confidence interval [CI], 50.5-138.8) versus 482 (95% CI, 411-566), P < 0.001}. In a multivariable analysis, mycophenolic acid (MPA) dose and hemoglobin level were found to be independent predictors for antibody response in RTR. A positive response rate of 27% versus 63% was observed in patients on and off MPA, respectively. An increase in MPA dose by 1 mg/kg weight reduced the odds for a positive response by 17% (odds ratio = 0.83; 95% CI, 0.75-0.92; P < 0.001). Geometric mean titers for RBD IgG were significantly reduced as MPA daily dose increased. Hemoglobin blood level <13 g/dL reduced the antibody response by 63% ( P = 0.04). Pain at the injection site after the second vaccine dose was significantly higher in the responders versus nonresponders (20.5% versus 5.5%, P = 0.01). Conclusions. Only 35% of RTR develop NA to the BNT162b2 mRNA vaccine. MPA is a major suppressor of antibody response in RTR.

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

“…Most studies assessed anti-SARS-CoV-2 immunity through an immunoassay to detect antibodies targeted at the spike protein, including some targeting specifically the receptor-binding domain (RBD) of the spike protein. Thirty studies reported neutralization assay results in addition to anti-SARS-CoV-2 antibody assays [ 34 , 37 , 41 , 48 , 51 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] ]. Thirty-one studies provided data on cellular immunity [ 17 , 21 , 22 , 34 , 37 , 41 , 45 , 46 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , 72 , [74] , [75] , [76] , [77] , [79] , [80] , [81] , [82] , [83] , [84] ].…”

“…Forty-seven studies described immunogenicity across various solid organ transplant populations ( n = 5974), mostly in kidney transplant recipients ( n = 3534, 59.2%) ( Table S5 ) [ 18 , [20] , [21] , [22] , [23] , [24] , [25] , [26] , 29 , 34 , 40 , [56] , [57] , [58] ], [ 62 , 63 , 65 , 66 , 69 , 72 , 73 , 75 , 77 , 79 , 81 , 120 , 126 ], [ [136] , [137] , [138] , [139] , [140] , [141] , [142] , [143] , [144] , [145] , [146] , [147] , [148] , [149] , [150] , [151] , [152] , [153] , [154] , [155] , [156] , [157] , [158] , [159] , [160] ]. Twenty-four of those studies included a control group representing overall 1399 participants [ 21 , 34 , 57 , 63 , 66 , 69 , 72 , 73 , 75 , 79 , ...…”

“…Eleven studies reported results of neutralization assays [ 34 , 63 , 66 , 69 , 72 , 77 , 79 , 126 , 145 ]. Non-response rates were close to those in anti-S assays in most studies [ 63 , 72 , 77 , 126 ], while several studies performed the assay only in anti-spike antibody positive participants who mostly tested positive in neutralization assays [ 69 , 79 , 145 ].…”

“…Solid organ transplant-specific treatments (calcineurin inhibitors, antimetabolites, corticosteroids) were often associated with a higher non-response rate or lower antibody titres [ 20 , 21 , 24 , 40 , 56 , 62 , 65 , 69 , 72 , 75 , 81 , 136 , [138] , [139] , [140] , [141] , [142] , 144 , 145 , 148 , [154] , [155] , [156] , [157] , 159 , 160 ] ( Table S5 ). Older age and lower estimated glomerular filtration rate were repeatedly associated with a non-responder status [ 21 , 24 , 79 , 120 , 138 , 142 , 144 , 155 ].…”

Antibody Response to mRNA Vaccines against SARS-CoV-2 with Chronic Kidney Disease, Hemodialysis, and after Kidney Transplantation

“…The extent to which S1-AB titer correlates with protection against infection and severe COVID-19 courses is incompletely understood. An interesting point was raised in recent publications: while the development of positive AB titers seems to correlate reasonably well with neutralizing antibodies [ 39 ] and neutralizing capacity of patient plasma [ 40 ], 10% of seropositive KTRs did not develop neutralizing capacity [ 39 ]. Comparison and interpretation of cellular assays is difficult due to the heterogeneity of employed analyses.…”