Previous studies have demonstrated that mice deficient in the macrophage migration inhibitory factor (MIF) gene are protected from ovariectomy (OVX)-induced bone loss. We developed a novel MIF-deoxyribonucleic acid (DNA) vaccine by introducing oligonucleotides encoding a helper T epitope into the cDNA sequence of murine MIF Mice given the MIF-DNA vaccine produced high titers of autoantibody against MIF, and were protected from OVX-induced bone loss. Our results further support the hypothesis that MIF is involved in the pathomechanism of OVX-induced bone loss, and also show that active immunization against MIF using a DNA vaccine may be useful for the prophylactic treatment of postmenopausal osteoporosis. (c) 2007 Elsevier Ltd. All rights reserved.