Leishmania major causes mild to severe cutaneous lesions resulting in significant disfigurations, if untreated. The drugs are toxic and drug-resistance parasites are emerging. Therefore, a prophylactic vaccination is an urgent need. As no vaccine is available, we compared the genes expressed by virulent and avirulent parasites. We identify L. major adenylate kinase (AdeK) as a probable vaccine candidate after a series of experimentations. We cloned the gene in mammalian pcDNA6/HisA and pet28a+ vector for in vivo expression following immunization and in vitro protein expression for booster, respectively. We observed that immunization of susceptible BALB/c mice with AdeK resulted in significant protection against L. major challenge infection. The protection was accompanied increased IFN-γ producing lymphoctyes and reduced IL-4, IL-17 and IL-10 secreting central and effector Th2, Th17 and Treg memory cells respectively. These observations indicate L. major AdeK as a potential vaccine candidate.