24Background. Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue 25 infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study 26 was to investigate the vaccine potential of two previously described immunogenic M. 27 ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU. 28 Methods. Recombinant versions of the two proteins were each electrostatically coupled with a 29 previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were 30 vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged 31 with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-32 to-ulceration compared to unvaccinated mice. 33 Results. The MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies 34 that were predominately subtype IgG 1 . However, all mice developed ulcers by day-40 post-M. 35 ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration 36 between the experimental vaccine groups and unvaccinated animals.37