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Objective: To study the role of antibodies in protection against Leishmania tropica (L. tropica) infection in the experimental model of BALB/c mice.Methods: BALB/c mice were vaccinated against L. tropica by soluble Leishmania antigen or recombinant L. tropica stress-inducible protein-1 (LtSTI1) of L. tropica, and against Leishmania major (L. major) by soluble Leishmania antigen. Monophosphoryl lipid A was used as an adjuvant. The L. tropica- or L. major-vaccinated mice were challenged by L. tropica or L. major, respectively. The levels of anti-Leishmania antibodies (IgG1 and IgG2a) were determined after vaccination and after challenge. Results: All vaccinated groups caused a higher antibody response in comparison with the control group. The L. major-vaccinated group showed lower IgG1 response than the control group after the challenge. Conversely, in L. tropica-vaccinated mice, the levels of antibodies were higher than the control group. Moreover, the group receiving rLtSTI1 and monophosphoryl lipid A showed higher levels of antibodies than those of the rLtSTI1 group. In vaccinated mice, antibody responses against L. tropica remained high until 16 weeks after the challenge. Conclusions: The higher levels of post-challenge antibodies are associated with protective vaccination against L. tropica infection of BALB/c mice. Our findings provide new insight into the association of antibody with vaccine-induced protective immunity against L. tropica infection. More studies are needed to clarify the role of antibody in protection against L. tropica.