## 4 Discussion  
In this study, we evaluated the efficacy and safety of the vaccine anti SARS-CoV-2 in transplant patients under immunosuppressive treatment. Immunosuppressants, usually used to reduce the immune activity in patients after organ transplant, could both increase the risk of viral load and reduce the immunogenicity of vaccines. In a recent study, [PERSON] et al. [10] documented that in patients >65 years of age, the use of mycophenolate and the mammalian target of rapamycin inhibitors in the post-transplant period were associated with decreased serologic response to influenza vaccines. To reduce the risk of losing the effectiveness of vaccines, in transplanted patients, there is a widespread practice of reducing anti-rejection with the increased probability of inducing graft rejection [11]. Data recorded using other vaccines may not be translated to the novel vaccines deployed for SARS-CoV-2. In our study, comparing the TDM values of the immunosuppressiveants during the study with those of the same patients before the COVID-19 pandemic period, we did not evaluate any difference. In fact, as reported in the clinical records of each patient, the daily definite dose of the immunosuppressiveants was not modified during the vaccination period. A reduced seroconversion rate after one vaccination in patients with kidney transplant [12] and in patients treated with immunosuppressiveants was also observed [13]. [PERSON] et al. [14], in 140 patients treated with immunosuppressiveant drugs for autoimmune rheumatic and glomerular diseases and evaluated both the serological and T-cell response after the first and the second-dose of SARS-CoV-2 vaccine, documented the immunogenicity of SARS-CoV-2 vaccination. [PERSON] et al. [15], in an observational study, found that 301 transplanted patients (46%) had no antibody response following dose 1 or 2 of the SARS-CoV-2 mRNA vaccines. In our study, we documented that SARS-CoV-2 vaccination induced a dose- and gender-related serological response. In the present study, the vaccine caused a dose- and gender-related serological response. In fact, we documented an increased response 1 month after the second dose and after the booster dose. In 63.6% of the enrolled patients, we documented a significant serological response at T2, particularly in women. In fact, in our study, we found that women presented significantly higher levels of IgG with respect to men, three and six months after the II dose of the vaccine (T3 and T4) and after the booster dose (T5). Even if we were not able to demonstrate the role of gender on immune response, this could represent a limitation of our study, so we can suppose that both sex hormones and the gene expression off the X chromosome could be involved in this difference. In particular, [PERSON] et al. [16] documented that the X chromosome is involved in immune functions such as the Toll-like receptor 7, CD40 ligand, and forkhead box P3, which could explain this difference. However, we also cannot exclude that this difference may be related to the small sample size, and this represents another limitation of the present study. Moreover, our data agreed with the clinical study of [PERSON] et al. [17], which suggested to not delay the second dose beyond 21 days from the first vaccination dose. In our study, we also documented that the serological response decreased with a time-dependent pattern, particularly 6 months after the second dose. The booster induced an increase in immunological response in 24 patients (72.7%). Finally, in these patients, we did not record the development of ADRs related to the vaccine. At the end of the study, six patients developed COVID-19, but we failed to find a correlation with respect to the age or gender. Only in one patient did the vaccine not induce the stimulation of SARS-CoV-2 antibodies. In conclusion, the vaccine anti SARS-CoV-2 is immunogenic in patients under immunosuppressive, and is not related to the development of ADRs.