Vaccine composition containing a mutant of the human Interleukin-15 (IL-15). The use of said mutant polypeptide of human IL-15 to manufacture a medicament for the active immunotherapy of diseases associated with IL-15 overexpression, including some autoimmune diseases and hematological malignancies. Administration to an individual that needs it of a therapeutically effective amount of the vaccine, that comprises the mutant polypeptide of the human IL-15 of the invention, constitutes a method for the therapy of IL-15 over-expressing related diseases.