Impact of Moderna mRNA-1273 Booster Vaccine on Fully Vaccinated High-Risk Chronic Dialysis Patients after Loss of Humoral Response

Abstract

The long-term effect of protection by two doses of SARS-CoV-2 vaccination in patients receiving chronic intermittent hemodialysis (CIHD) is an urging question. We investigated the humoral and cellular immune response of 42 CIHD patients who had received two doses of SARS-CoV-2 vaccine, and again after a booster vaccine with mRNA-1273 six months later. We measured antibody levels and SARS-CoV-2-specific surrogate neutralizing antibodies (SNA). Functional T cell immune response to vaccination was assessed by quantifying interferon-γ (IFN-γ) and IL-2 secreting T cells specific for SARS-CoV-2 using an ELISpot assay. Our data reveal a moderate immune response after the second dose of vaccination, with significantly decreasing SARS-CoV-2-specific antibody levels and less than half of the study group showed neutralizing antibodies six months afterwards. Booster vaccines increased the humoral response dramatically and led to a response rate of 89.2% for antibody levels and a response rate of 94.6% for SNA. Measurement in a no response/low response (NR/LR) subgroup of our cohort, which differed from the whole group in age and rate of immunosuppressive drugs, indicated failure of a corresponding T cell response after the booster vaccine. We strongly argue in favor of a regular testing of surrogate neutralizing antibodies and consecutive booster vaccinations for CIHD patients to provide a stronger and persistent immunity.

Keywords: COVID-19; SARS-CoV-2; T cell response; booster; hemodialysis; mRNA-1273; seroconversion; vaccination.

Figure 1

Illustration of the study setup. Samples were collected at three different time points to evaluate the dynamic of the patients’ immunization status by different immunoassays. Abbreviations: CIHD (chronic intermittent hemodialysis); S-RBD (spike receptor binding domain); ELISpot (enzyme-linked immunospot).

Figure 2

Antibody response in plasma samples of patients taken at three different time points (t₀ = four weeks after second dose, t₁ = six months after second dose and t₂ = 14 days after third dose (=booster vaccine) of mRNA-1273 (Moderna)). Abbreviations: S-RBD-ab (spike receptor binding domain-antibodies); SNA (surrogate neutralizing antibodies). Data are expressed as median (IQR). * p ≤ 0.05, *** p ≤ 0.001, **** p ≤ 0.0001 (Friedman test).

Figure 3

Proportion of patients with strong (dark blue: >500 BAU/mL or >70%-INH), moderate (light blue: 100–500 BAU/mL or 50–70%-INH) and no/low (red: <100 BAU/mL or <50%-INH) humoral response at the three different time points (t₀, t₁ and t₂). Data are expressed as percentage. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001 compared to t₀; ^### p ≤ 0.001 compared to t₁.

Figure 4

Fraction of neutralizing capacity for different antibody levels. The inner circle is showing levels of antibody response (BAU/mL) with the corresponding percentage of neutralizing antibodies (%-INH) in the outer circle for t₀, t₁ and t₂, respectively. Data are expressed as percentages. Applying the following antibody and SNA cut-off levels: negative (<7.1 BAU/mL or <30%-INH), borderline (>7.1–8.5 BAU/mL or >30–35%-IHN), low (>8.5–100 BAU/mL or >35–50%-INH), moderate (>100–500 BAU/mL or >50–70%-INH), strong (>500 BAU/mL or >70%-INH).

Figure 5

Cytokine profile of T cell response specific to SARS-CoV-2 at different time points and in comparison to a healthy control group. Abbreviations: ELISpot (enzyme-linked immunospot); ctrl (control); IFN-γ (Interferon-γ); IL-2 (Interleukin-2). Data are expressed as median (IQR). Intragroup paired analysis: * p ≤ 0.05, ** p ≤ 0.01 as indicated (Kruskal–Wallis test).