Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression

Abstract

Objective: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination.

Methods: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases.

Results: Following first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy.

Conclusion: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.

Keywords: B-lymphocytes; COVID-19; autoimmune diseases; rituximab; vaccination.

Figure 1

Humoral responses to SARS-CoV-2 vaccination in IS patients. (A) Anti-S titre at baseline, following first-dose and second-dose vaccine in patients who were infection-naïve. (B) Anti-S titre by B-cell status at the time of vaccination in infection-naïve patients at baseline, 28–40 days following first-dose vaccine and 18–29 days after second-dose vaccine. (C) Anti-S titre by vaccine type at the time of vaccination in infection-naïve patients at baseline, 28–40 days following first-dose vaccine and 18–29 days after second-dose vaccine. (D) Anti-S titre following first-dose and second-dose vaccinations in healthy volunteers (HVs), IS patients and a matched cohort of IS patients. (E) Correlation of anti-S titre after second-dose vaccination and B-cell count at the time of vaccination in IS patients. (F) Anti-S titre in patients with previous natural infection at baseline, following first-dose and second-dose vaccines. Dotted line indicates 7.1 BAU/mL, the threshold for detectable anti-S antibodies. For visualisation of data on a log scale, values=0 are represented by 0.001, which is below the lower limit of the assay (0.00142). HV, healthy volunteer; IS, immunosuppressed; S, spike. **p<0.01, ***p<0.001, ****p<0.0001.

Figure 2

Cellular responses to SARS-CoV-2 vaccination in IS patients. (A) T-cell responses to spike protein peptides of SARS-CoV-2 in infection-naïve patients at baseline, 28–40 days following first-dose vaccine and 18–29 days after second-dose vaccine. (B) T-cell responses in those receiving tacrolimus therapy versus those who were not in infection-naïve participants at baseline, after first-dose vaccine and after second-dose vaccine. (C) T-cell responses by vaccine type in infection-naïve participants at baseline, after first-dose vaccine and after second-dose vaccine. (D) T-cell responses following first-dose and second-dose vaccinations in healthy volunteers (HVs), IS patients and a matched cohort of IS patients. (E) T-cell responses following second-dose vaccine in those who did and did not also seroconvert. (F) Correlation of T-cell responses after second-dose vaccination and age at time of vaccination. Dotted line indicates mean plus 3 SDs for spike peptide pool reactivity calculated from infection-naïve, non-vaccinated individuals (40 SFU/10⁶ PBMC). For visualisation of data on a log scale, values=0 are represented by 0.1. HV, healthy volunteer; IS, immunosuppressed; PMBC, peripheral blood mononuclear cell; SFU, spot-forming unit.