Immunogenicity of ChAdOx1 nCoV-19 vaccine after a two-dose inactivated SARS-CoV-2 vaccination of dialysis patients and kidney transplant recipients

Abstract

Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1-2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4-26.8), 1092.5 (606.9-1927.2), and 1740.9 (1106-3762.3) BAU/mL, and percent neutralization was 0.9 (0-9.9), 98.8 (95.9-99.5), and 99.4 (98.8-99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p < 0.05). Seroconversion and neutralization positivity rates in PD, HD, and control groups were 100% but were impaired in KT patients (39% and 16%, respectively). S1-specific T-cell counts were increased in PD and HD groups (p < 0.05) but not in KT patients. The positive S1-specific T-cell responder rate was > 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p < 0.05). The heterologous inactivated virus/ChAdOx1 nCoV-19 vaccination strategy elicited greater immunogenicity among dialysis patients; however, inadequate responses remained among KT recipients (TCTR20210226002).

Figure 1

Humoral and cell-mediated immune responses in kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients and healthy individuals (controls) who received two doses of inactivated vaccine (V2) compared with those receiving a third dose of ChAdOx1 nCoV-19 vaccine (V3). (a) Anti-receptor-binding domain (RBD) antibody levels at two weeks after V2 and V3 are presented in log10 binding antibody units (BAU)/mL using scatter dot plots. Each dot represents an individual participant, and horizontal lines indicate the median and interquartile range. The dotted line indicates the threshold value of 7.1 BAU/mL. (n = 106) (b) Anti-RBD antibody levels at two weeks after V2 and V3 within individuals are shown. (n = 106) (c) The percent neutralization inhibition at two weeks after V2 and V3 are presented. The dotted line indicates the 35% threshold for neutralization positivity. (n = 106) (d) SARS-CoV-2–specific, IFN-γ-producing T-cell responses to the S1 protein at two weeks after V2 and V3 are presented in the scatter dot plots. (n = 106) Horizontal lines indicate the median and interquartile range. The dotted line indicates the threshold value of 6 SFUs/10⁶ PBMCs. *P-value < 0.05. IFN-γ, interferon-γ; SFU, spot forming unit; NS, non-significant; PBMCs, peripheral blood mononuclear cells; S, spike glycoprotein; S1, S1 domain of spike protein.

Figure 2

Solicited adverse events on days 3 and 7 after (a) the second dose of inactivated SARS-CoV-2 vaccine (V2) and (b) the additional dose of ChAdOx1 nCoV-19 vaccine (V3). HD, hemodialysis; KT, kidney transplant; PD, peritoneal dialysis; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2.