To determine the safety and protective efficacy of a C. muridarum MOMP vaccine, formulated with CpG-1826 and four different concentrations of Montanide ISA 720 VG (70%, 50%, 30% and 10%), BALB/c mice were immunized twice intramuscularly. Local reactogenicity was significant for vaccines formulated with 70% and 50% Montanide but not in mice receiving 30% and 10% Montanide. Robust humoral and cell mediated memory immune responses were elicited by the 70%, 50% and 30% Montanide formulations. Mice were challenged intranasally with C. muridarum and, at day 10 post-challenge, mice were euthanized. Based on changes in body weight, lung's weight and number of IFU recovered, mice vaccinated with the 70%, 50% and 30% Montanide formulations were significantly protected, but not mice receiving 10% Montanide. To conclude, we recommend the 30% Montanide concentration to be tested in humans and animal models to determine its safety and efficacy, in comparison to the 70% Montanide concentration currently used. The 30% Montanide formulation will significantly facilitate licensing for human use.