Heterologous immunization with BNT162b2 followed by mRNA-1273 in dialysis patients: seroconversion and presence of neutralizing antibodies

Abstract

Introduction The vital renal replacement therapy makes it impossible for dialysis patients to distance themselves socially. This results in a high risk of SARS-CoV-2 infection and developing COVID-19 with excess mortality due to disease burden and immunosuppression. We determined the efficacy of a 100 µg booster of mRNA-1273 (Moderna, Inc., Cambridge, Massachusetts, USA) 6 months after two doses of BNT162b2 (BioNTech/Pfizer, Mainz, Germany/New York, NY, USA) in 194 SARS-CoV-2 naïve dialysis patients. Methods Anti-SARS-CoV-2-spike antibodies were measured with the Elecsys® Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH, Germany) 4 and 10–12 weeks after two doses of BNT162b2 as well as 4 weeks after the mRNA-1273 booster. The presence of neutralizing antibodies was measured by the SARS-CoV-2 Surrogate Virus Neutralization Test (GenScript Biotech, USA). Two different cut-offs for positivity were used, one according to the manufacturer's specifications and one correlating with positivity in a plaque reduction neutralization test (PRNT). ROC analyses were performed to match the anti-SARS-CoV-2-spike antibody cut-offs with the cut-offs in the surrogate neutralization assay accordingly. Results Any level of immunoreactivity determined by anti-SARS-CoV-2-spike antibody assay was found in 87.3% (n = 144/165) and 90.6% (n = 164/181) 4 and 10–12 weeks after two doses of BNT162b2. This was reduced to 68.5% or 60.6% 4 weeks and 51.7% or 35.4% 10–12 weeks, respectively, when using the ROC revealed cut-offs for neutralizing antibodies in the surrogate neutralization test (manufacturer given cut-off ≥ 103 U/ml and cut-off correlating with PRNT ≥ 196 U/ml). Four weeks after the mRNA-1273 booster, the concentration of anti-SARS-CoV-2-spike antibodies increased to 23 119.9 U/ml and consecutively to 97.3% for both cut-offs of neutralizing antibodies. Conclusion Two doses of BNT162b2 followed by one dose of mRNA-1273 within 6 months in patients receiving maintenance dialysis resulted in significant titers of SARS-CoV-2-S-Ab. While two doses of mRNA vaccine only achieved adequate humoral immunity in a minority, the third vaccination boosts the development of virus-neutralizing quantities of SARS-CoV-2 spike antibodies (against wild type SARS-CoV-2) in almost all patients.

SARS-CoV-2-Spike Antibody and T-Cell Responses Elicited by a Homologous Third mRNA COVID-19 Dose in Hemodialysis and Kidney Transplant Recipients

“…These studies showed a booster effect of variable size in the two group populations. Among KTR who failed to develop detectable antibodies after the second vaccine dose, the percentage of responders after 3D varied substantially across the studies [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Fewer studies have assessed the impact of the receipt of 3D on SARS-CoV-2-S-targeted functional T-cell responses [5,[18][19][20][21][22], which crucially contribute to providing protection against SARS-CoV-2 infection.…”

SARS-CoV-2 neutralizing antibody response after three doses of mRNA1273 vaccine and COVID-19 in hemodialysis patients

“…Our research in hemodialysis patients demonstrated a strong vaccinal nAb response to MOD-MOD-MOD and an even stronger one post-COVID-19. Although plaque reduction neutralization test (PRNT) is the preferred method for quantifying antibodies capable of neutralizing SARS-CoV-2 virus, multiple groups had extensively evaluated GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit (6,(14)(15)(16). It was demonstrated that GenScript sVNT ELISA method gives comparable results and good correlation to PRNT in the detection of nAbs.…”

“…Our study has several strengths. First, while previous reports addressed the nAb response to various homologous and heterologous triple vaccination schemes (6)(7)(8)(9)12), this is the first regarding nAb dynamics after MOD-MOD-MOD vaccination. Second, we quantitated in the same serum sample the nAb responses specific to both WT and Omicron.…”

“…Therefore, a third vaccination ("booster") is frequently administered to augment protection against coronavirus disease 2019 (COVID-19) in these patients. Previous reports described receptor-binding domain (RBD) immunoglobulin G (IgG) and neutralizing antibodies (nAbs) after three doses of vaccinations with AZD1222 (AZD; Oxford-AstraZeneca), BNT162b2 (BNT; Pfizer-BioNTech), or mRNA1273 (MOD; Moderna) following various regimens, such as BNT-BNT-MOD, BNT-BNT-BNT, and AZT-BNT-BNT in these dialysis patients (5)(6)(7)(8)(9). While MOD is widely used in hemodialysis patients, we are unaware of data on the nAb response to MOD-MOD-MOD.…”

SARS-CoV-2 Vaccination in Kidney Transplant Recipients—Stratified Analysis of the Humoral Immune Response

“…By correlating the SARS-CoV-2 antibody concentrations with the inhibitory power for binding of the wild-type spike protein to the ACE-2 receptor, we derived a cutoff value for a 30% virus neutralization that may be clinically meaningful for patients after kidney transplantation (Figure 3 ). The cutoff value largely corresponds to that in a recently examined dialysis cohort 13 and in the normal population as provided by the manufacturer. 14 However, not entirely unexpectedly and as far as comparable because 2 different test methods were used, the respective cutoff on basis of the live virus neutralization test for inactivation of the Omicron variant was 53 times higher.…”