Immunogenicity and reactogenicity of homologous mRNA-based and vector-based SARS-CoV-2 vaccine regimens in patients receiving maintenance dialysis

Abstract

Patients receiving maintenance dialysis (MD) are vulnerable to COVID-19-related morbidity and mortality. Currently, data on SARS-CoV-2-specific cellular and humoral immunity post-vaccination in this population are scarce. We conducted a prospective single-center study exploring the specific cellular (interferon-γ and interleukin-2 ELISpot assays) and humoral immune responses (dot plot array and chemiluminescent microparticle immunoassay [CMIA]) at 4 weeks and 6 weeks following a single dose or a complete homologous dual dose SARS-CoV-2 vaccine regimen in 60 MD patients (six with a history of COVID-19). Our results show that MD patients exhibit a high seroconversion rate (91.7%) but the anti-spike IgG antibodies (CMIA) tend to wane rapidly after full immunization. Only 51.7% of the patients developed T cell immune response. High anti-spike IgG antibodies may predict a better cellular immunity. While patients with prior COVID-19 showed the best response after one, SARS-CoV-2-naïve patients may benefit from a third vaccine injection.

Keywords: Cellular immune response; Hemodialysis; Immunoglobulins; Peritoneal dialysis; T cells.

Fig. 1

Vaccine-induced SARS-CoV-2-specific IL-2 (A) and IFN-γ (B) and IL-2 and/or IFN-γ (C)-producing T cells and SARS-CoV-2 anti-spike IgG antibodies as determined using the Abbott assay (D), GenID assay (E), and both (F) at T1 and T2. A) T1 (n = 50): Not reactive, 21 (42.0%); borderline, 6 (12.0%); reactive, 18 (36.0%); invalid, 5 (10.0%). T2 (n = 58): Not reactive, 21 (36.2%); borderline, 6 (10.3%); reactive, 15 (25.9%); invalid, 16 (27.6%). T1 vs. T2 (p = 0.73). B) T1 (n = 50): Not reactive, 37 (74.0%); borderline, 0 (0.0%); reactive, 11 (22.0%); invalid, 2 (4.0%). T2 (n = 58): Not reactive, 34 (58.6%); borderline, 4 (6.9%); reactive, 14 (24.1%); invalid, 6 (10.3%). T1 vs. T2 (p = 0.12). C) T1 and/or T2 (n = 60): Not reactive, 20 (33.3%); borderline, 6 (10.0%); reactive, 31 (51.7%); invalid, 3 (5.0%). D) T1 (n = 50): Positive, 44 (88.0%)^a; negative, 6 (12.0%)^b. T2 (n = 58): Positive, 52 (89.7%)^a; negative, 6 (10.3%)^b. T1 vs. T2 (p = 1.0)^e. E) T1 (n = 49): Positive, 44 (89.8%)^c; negative, 5 (10.2%)^d. T2 (n = 58): Positive, 53 (91.4%)^c; negative, 5 (8.6%)^d. T1 vs. T2 (p = NS)^e. F) T1 and/or T2 (n = 60): Positive, 55 (91.7%); negative, 5 (8.3%). The dashed horizontal lines indicate the cut-off for positivity (reactive); the area between the horizontal lines indicates the borderline zone used in each GenID assay. ^aPositive refers to antibody levels >16%. ^bNegative refers to antibody levels ≤16%. ^cPositive refers to antibody concentration > 50 AU/mL. ^dNegative refers to antibody concentration ≤ 50 AU/mL. ^eMcNemar's test for paired nominal data was used. IFN-γ, interferon-γ; IL-2, interleukin-2; SARS-CoV-2, NS, not significant; severe acute respiratory syndrome-coronavirus type-2; T1, timepoint 1; T2, timepoint 2.

Fig. 2

Vaccine-induced SARS-CoV-2-specific IL-2- and IFN-γ-producing T cells and SARS-CoV-2 anti-spike IgG antibodies as determined using the GenID assay at T1 and T2, stratified by mRNA vaccine regimen (A–C), vector-based vaccine regimen (D—F), for infection naïve patients, or booster vaccination in patients with a history of SARS-CoV-2 infection (G–I). A) IL-2: T1 (n = 37): Not reactive, 17 (45.9%); borderline, 6 (16.2%); reactive, 12 (32.4%); invalid, 2 (5.4%). T2 (n = 44): Not reactive, 17 (38.6%); borderline, 4 (9.1%); reactive, 11 (25.0%); invalid, 12 (27.3%). B) IFN-γ: T1 (n = 37): Not reactive, 32 (86.5%); borderline, 0 (0%); reactive, 4 (10.8%); invalid, 1 (2.7%). T2 (n = 44): Not reactive, 30 (68.1%); borderline, 2 (4.5%); reactive, 9 (20.5%); invalid, 3 (6.8%). C) IgG: T1 (n = 37): Positive, 32 (86.5%)^a; negative, 5 (13.5%)^b. T2 (n = 44): Positive, 39 (88.6%)^a; negative, 5 (11.4%)^b. D) IL-2: T1 (n = 7): Not reactive, 3 (42.9%); borderline, 0 (0%); reactive, 1 (14.3%); invalid, 3 (42.9%). T2 (n = 9): Not reactive, 3 (33.3%); borderline, 1 (11.1%); reactive, 1 (11.1%); invalid, 4 (44.4%). E) IFN-γ: T1 (n = 7): Not reactive, 5 (71.4%); borderline, 0 (0%); reactive, 1 (14.3%); invalid, 1 (14.3%). T2 (n = 9): Not reactive, 4 (44.4%); borderline, 1 (11.1%); reactive, 1 (11.1%); invalid, 3 (44.4%). F) IgG: T1 (n = 7): Positive, 6 (85.7%)^a; negative, 1 (14.3%)^b. T2 (n = 9): Positive, 8 (88.9%)^a; negative, 1 (11.1%)^b. G) IL-2: T1 (n = 6): Not reactive, 1 (16.7%); borderline, 0 (0%); reactive, 5 (83.3%); invalid, 0 (0%). T2 (n = 5): Not reactive, 1 (20.0%); borderline, 1 (20.0%); reactive, 3 (60.0%); invalid, 0 (0%). H) IFN-γ: T1 (n = 6): Not reactive, 0 (0%); borderline, 0 (0%); reactive, 6 (100%); invalid, 0 (0%). T2 (n = 5): Not reactive, 0 (0%); borderline, 1 (20.0%); reactive, 4 (80.0%); invalid, 0 (0%). I) IgG: T1 (n = 6): Positive, 6 (100%)^a; negative, 0 (0%)^b. T2 (n = 5): Positive, 5 (100%)^a; negative 0 (0%)^b. All individuals with a history of SARS-CoV-2 infection were vaccinated with one dose of mRNA- BNT162b2 (n = 6). The dashed horizontal lines indicate the cut-off for positivity (reactive); the area between the horizontal lines indicates the borderline zone used in each GenID assay. ^aPositive refers to antibody levels >16%. ^bNegative refers to antibody levels ≤16%. IgG, immunoglobulin G; IFN-γ, interferon-γ; IL-2, interleukin-2.