As summarized in the current review, tremendous progress has been made in understanding (1) the entry process of MERS-CoV into target cells, (2) the structure and function of S glycoprotein and cellular receptor DPP4 in mediating viral entry, (3) antibody response during natural infection and isolation of broad and potent neutralizing mAbs, and (4) design and development of vaccine candidates using various innovative technologies. Here, DPP4 is linked to infection.