Delayed Humoral Response After 2 Doses of the BNT162b2 Vaccine in a Belgian Kidney Transplant Cohort.

We previously published disappointing results regarding the humoral response 28 d after the second dose of the BNT162b2 (Pfizer) vaccine in kidney transplant recipients (KTRs).[1]

The present article reports the serological response rate 90 d after the second injection using an immunoassay detecting antibody (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; upper limit of detection 250 U/mL). This work received institutional review board approval.

Eighty-two patients were included. None had a history of coronavirus disease 2019 infection and all tested negative for anti–severe acute respiratory syndrome coronavirus 2 nucleocapsid Ab. The median age was 60 (range, 18–84) y; 58% were male. The median time since transplantation was 113 (range, 8–439) mo. Fifty percent were treated with an association of tacrolimus, mycophenolate, and steroids.

The humoral response rates and mean anti-RBD Ab titers were 50% versus 70.7% (P = 0.010) and 45.2% (95% confidence interval, 27.7-62.8) versus 66.3% (95% confidence interval, 45.9-86.7) U/mL (P < 0.001), at day 28 and 90, respectively (Figure 1A and B). Forty-six percent (n = 38) of KTRs showed increased anti-RBD Ab titers at day 90 compared with day 28. These patients had similar baseline characteristics to KTRs whose Ab titers remained stable or decreased at day 90. Seventeen of 41 patients (41%) who had no humoral response at day 28 mounted a serological response at day 90. Overall, 24 patients (29%) did not have any serological response following vaccination. The characteristics of these patients did not differ from those who showed a serological response.

FIGURE 1.

Evolution of anti-RBD Ab response rate (A) and titers (B) between d 28 and 90 after the second dose of vaccine. Statistic comparisons between humoral response rates (A) were performed using the Fisher exact test. Ab, antibody; RBD, receptor-binding domain.

These results suggest that some KTRs show delayed kinetics of anti-RBD Ab after 2 doses of the mRNA BNT162b2 vaccine, contrasting with what has been observed in the general population, in whom the peak of humoral immunity appears earlier.[2] Indeed, Shrotri et al demonstrated in a cohort of 552 severe acute respiratory syndrome coronavirus 2–naive individuals an antispike Ab peak between 21 and 41 d after the second dose of the BNT162b2 or ChAdOx1 vaccine, followed by a significant decrease.[2] We might hypothesize to explain the delayed humoral response in our population of KTRs that immunosuppressive drugs decrease the activation and proliferation of CD4 T helper cells, leading to delayed interactions between T and B cells in lymph nodes.

Recent evidence emerged from the literature regarding the efficacy of the third dose of mRNA vaccine in KTRs.[3-5] Notably, a recently published placebo-controlled randomized trial including 120 KTRs demonstrated that a booster third dose of the mRNA-1273 vaccine given 2 mo after the second dose was associated with higher rates of seroconversion, anti-RBD Ab titers, and virus neutralization 1 mo after injection compared with placebo.[5] Interestingly, in line with our findings, the authors found that a subgroup of patients who received placebo showed mild increases in Ab titers.[5]

Our study adds interesting findings pointing out that some KTRs might naturally develop a delayed humoral response after 2 doses of mRNA vaccine. Still, Ab titers reached 3 mo after the second injection in our cohort remained weak, justifying a third-dose vaccine injection to promote humoral response.