Evidence of cell-mediated immune response in kidney transplants with a negative mRNA vaccine antibody response

To the editor:

Benotmane et al. have demonstrated that only 48% of renal transplant patients (RTxP) develop a serologic response after vaccination with an mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine.¹ Likewise, we reported that only 22% of RTxP develop anti–SARS-CoV-2 IgG after vaccination with the mRNA-based SARS-CoV-2 vaccine BNT162b2 (Pfizer-BioNTech).² To further characterize the immunologic response, we measured the cellular response to BNT162b2 vaccination in 7 RTxP with triple immunosuppression lacking anti–SARS-CoV-2 IgG after vaccination with 2 dosages of BNT162b2 (measured 18–60 days after the second dose). For that purpose, peripheral blood mononuclear cells were isolated from patients and stimulated with overlapping peptide pools for the SARS-CoV-2 spike protein, according to previously published protocols.³ In all 7 patients, S-protein–reactive T-helper cells were detected (Figure 1 ). All patients harbored interleukin-2–producing S-protein–reactive T-helper cells (Figure 1; 39% ± 11% of S-protein–reactive T-helper cells), and in 6 of the 7 patients, interferon-γ–positive S-protein–reactive T-helper cells were present (13% ± 11% of S-protein–reactive T-helper cells).

Figure 1.

S-protein–reactive T-helper cells in renal transplant patients after vaccination. (a) Peripheral blood mononuclear cells were freshly isolated from whole blood and cultured for 16 hours in the presence of overlapping peptide pools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and brefeldin A. T cells coexpressing CD154 and CD137 were defined as S-protein–specific. The cytokine profile of S-protein–specific T cells was characterized, and interleukin-2 (IL-2)/interferon-γ (IFN-γ) expression was determined. (b) In all 7 patients, S-protein–specific T-helper cells were detectable. (c) S-protein–specific T-helper cells produced IL-2 and IFN-γ. Pos, positive.

Thus, in all of the 7 RTxP, a cellular S-protein–specific immune response was induced by vaccination, despite the lack of S-protein–specific antibodies. The presence of a vaccine-induced T-cell response indicates that mRNA vaccines may well confer T cell–mediated vaccine-specific immunity in immunocompromised patients. Taken together, these findings underscore the importance for a comprehensive immune monitoring and the need for individualized schemes for booster vaccinations in this susceptible patient cohort.