Immunogenicity of Anti-SARS-CoV-2 Vaccination After Kidney Transplantation in Kidney Transplant Recipients Vaccinated Before Transplantation.

Abstract

Solid-organ transplant patients, including kidney transplant recipients (KTRs) are at high risk of severe forms of coronavirus disease 2019 (COVID-19) infection1 and fail to mount a robust and sustained humoral response to COVID-19 vaccines,2 despite reinforced schemes (Reference S1, SDC, https://links.lww.com/TP/C770).3 In this context, the use of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies, because preexposure prophylactic strategy has been dramatically helpful to provide passive protection against COVID-19. However, currently available monoclonal antibodies are no longer effective at neutralizing the most recent Omicron variants of SARS-CoV-2.4,5 Hence, vaccination is the unique remaining prophylactic tool against COVID-19 in vulnerable individuals. Unlike KTRs, patients with chronic kidney disease, including those undergoing long-term dialysis, have shown potent vaccine responses against SARS-Cov-2, reaching antibody levels close to those observed in the general population (Reference S3, SDC, https://links.lww.com/TP/C770). Whether a pretransplant vaccination improves the response to subsequent doses after transplantation has yet to be established. To address this important question, we aimed to investigate the trajectory of the SARS-CoV-2-specific humoral immune response following a booster dose in KTRs who had received at least 2 vaccine shots before the transplantation. This retrospective single-center study (Necker Hospital, Paris, France) enrolled all consecutive patients, transplanted between June and December 2021, following a minimum of 2 vaccine doses before the kidney transplantation (KT), in the absence of concurrent immunosuppressive therapy. Forty-nine patients (25 men [51.0%], median age of 57.2 y, interquartile range 42.9–68.1) were enrolled (Table S1 and Material S1, SDC, https://links.lww.com/TP/C770). At time of KT, most patients (93.6%) displayed a positive SARS-CoV-2 serology and 66% showed an anti-Spike IgG titer >264 binding antibody unit (BAU)/mL (median titer of 809 [128.5–3210.0]). In the 26 KTRs who did not receive an additional vaccine shot after transplantation, antibody titers decreased to 131 BAU/mL at M3 and to 136 BAU/mL (24.5–662.5) at the last follow-up, after a median posttransplant time of 5.0 (3.0–6.9) mo (Table S1, SDC, https://links.lww.com/TP/C770). Twenty-three KTRs (46.9%) received a booster dose of messenger RNA COVID-19 vaccine after KT. The median time between KT and first dose was 13.4 wk (11.1–22.1). Nineteen (82.6%) received only 1 posttransplant dose, while 4 patients (17.4%) received an additional one. Most patients exhibited a strong postvaccinal humoral response after one injection: 20 patients (90.9%) showed a postvaccinal anti-Spike titer > 264 BAU/mL (versus 10 before vaccine) and anti-Spike IgG titers increased significantly from 172.0 (48.0–698.5) to 1220.0 (583.8–3299.5), P = 0.0004 (Figure 1). Compared to responders, the nonresponders (to one posttransplant dose) were significantly older, were given more frequently rituximab at induction, and had received a greater number of vaccine doses before KT (Table S2, SDC, https://links.lww.com/TP/C770). One of the nonresponders after the first dose developed an effective response after the second. Interestingly, a strong recall humoral response also occurred in KTRs treated with belatacept after one vaccine dose (anti-Spike IgG titers increased from 590.5 [118.3–987] to 3641.5 BAU/mL [2898.5–3819]), whereas belatacept was found to dramatically hamper the antibody response to COVID-19 vaccine in patients who were vaccine-naive at the time of transplantation (Reference S1, SDC, https://links.lww.com/TP/C770).2Figure 1.: Evolution of anti-SARS-CoV-2 spike IgG at day 0 postkidney transplantation, before and after 1 injection of anti-SARS-CoV-2 mRNA vaccination in 23 KTRs who received anti-SARS-CoV-2 vaccination before transplantation. BAU, binding antibody unit; KT, kidney transplantation; KTR, kidney transplant recipient; mRNA, messenger RNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.Eleven patients (22.4%) experienced COVID-19 after KT, including 2 breakthrough infections following posttransplant dose. All but one cases were infected with the Omicron variants (Delta variant in one case). Three patients were admitted to hospital, two of whom experienced a severe infection requiring intensive care unit and eventually died. These latter were infected with the Omicron variants, displayed a weak anti-spike response and were not administered preventive mAbs before COVID-19. Our study is limited by its retrospective nature, by the relatively small number of patients and the lack of data about neutralizing antibodies (which are a better measure of protection than the commercially available anti-spike antibody assay) and vaccine-specific cellular response. However, it clearly demonstrates that a pretransplant vaccination against COVID-19 before KT significantly improves the response to vaccine after KT. Anti-SARS-CoV-2 vaccination is recommended in dialysis patients, who are exposed to severe forms of COVID-19 (Reference S6, SDC, https://links.lww.com/TP/C770). Our data further stress the importance of vaccination in patients on the waiting list for solid-organ transplantation. Pretransplant priming of vaccine-specific responses can dramatically improve the posttransplant vaccine response through the recall stimulation of a preexisting memory response.