Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.