T-cell and Antibody Response After 2 Doses of the BNT162b2 Vaccine in a Belgian Cohort of Kidney Transplant Recipients

Disappointing results in the humoral response after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients (KTRs) have emerged from the literature.^1,2 In this context, exploring SARS-CoV-2-specific cellular response induced by vaccination is relevant.

We prospectively assessed the antibody (Ab) (with an immunoassay detecting Ab against the spike protein receptor-binding domain [RBD] [Elecsys anti-SARS-CoV-2, Roche Diagnostics GmbH, Mannheim, Germany—positive threshold >0.8 U/mL and upper limit of detection 250 U/mL]) and T-cell response (with a whole blood interferon-gamma [IFN-γ] release assay [IGRA] using the antigens of the SARS-CoV-2 spike protein to activate T cells, following manufacturer’s instructions [SARS-CoV-2 IGRA, Euroimmun, Lübeck, Germany—positive threshold >100 mIU/mL]) rates 1 mo after the second dose of the mRNA BNT162b2 vaccine (Pfizer-BioNTech), between April 17, 2021 and June 15, 2021, in a single-center cohort of KTRs. All patients signed informed consent and the study received institutional review board approval (B4032021000056).

Ninety KTRs were included (median age: 60 [range, 38–79] y, 48% female individual, and median time since transplantation: 102 [range, 9–440] mo). Fifty-one percent of patients were treated with an association of tacrolimus, mycophenolate, and steroids, and 24% received an antimetabolite-free regimen. Seven had a previous history of documented SARS-CoV-2 infection before vaccination.

One month after the second vaccine dose, 58 (64.4%) KTRs mounted a humoral response (mean [±SEM] anti-RBD Ab titer: 70.2 [±11.9] U/mL) and 29 (32.2%) displayed a cellular response (positive IGRA test) (mean [±SEM] IFN-γ value: 803.4 [±165.1] mUI/mL). Overall, 22 (24%) KTRs had both humoral and cellular responses, 7 (8%) had isolated cellular response, 36 (40%) had isolated humoral response, and 25 (28%) had no immune response.

The cellular response rate and IFN-γ values were not significantly different between Ab responders and Ab nonresponders (Figure 1A). However, KTRs displaying high Ab response (anti-RBD Ab titer >150 U/mL) had significantly higher cellular response rate and IFN-γ values compared with KTRs with a weaker-or no-Ab response (Figure 1A and B). Correlation between IFN-γ and Ab values (Figure 1C) was statistically significant (r = 0.666, P < 0.001, Pearson correlation test).

FIGURE 1.

A, Cellular response rate in the cohort. The cellular response rate was not significantly different between patients with antibody response and without antibody response (P = 0.138, χ² test). However, among patients with humoral response, those with high antibody response (anti-RBD titers >150 U/mL) showed higher rates of cellular response compared with others (P < 0.001, χ² test). B, IFN-γ values (mIU/mL) and antibody titers. Patients with antibody titers >150 U/mL had higher IFN-γ values than others (P = 0.049, Kruskal-Wallis test). C, Correlation between anti-RBD antibody titers and IFN-γ values (r = 0.666, P < 0.001, Pearson correlation test). IFN-γ, interferon-gamma; RBD, receptor-binding domain.

Reports on the T-cell response rate after anti-SARS-CoV-2 vaccination in KTRs are limited. Bertrand et al³ found a 57.8% T-cell response rate in 26 KTRs after 2 doses of the BNT162b2 vaccine, using an ELISpot immunoassay. Cucchiari et al⁴ reported a 54.7% rate after the second dose of the mRNA-1273 vaccine in 117 SARS-CoV-2 naive transplant patients, also using an ELISpot immunoassay. We found a lower rate (32%) that might be explained by the differences in sensitivity of the ELISpot test compared with IGRA ELISA as reported for the detection of latent tuberculosis infection.⁵

Interestingly, we found that 20% of Ab nonresponders have a T-cell response and 72% of KTRs showed either IFN-γ or Ab response. Moreover, KTRs with higher Ab response are more likely to develop a T-cell response. In that context, a third vaccine dose might help boost both cellular and serological responses. Larger studies are needed to characterize the cellular response and its clinical relevance.