Hemorrhagic septicemia (HS) is an important infectious disease in cattle and buffaloes, caused by Pasteurella multocida B:2 and E:2. The intranasal recombinant OmpH-based vaccine was successfully used to protect dairy cattle from HS in a previous study. Thus, this study aimed to examine the protective ability of that vaccine among buffaloes. Four groups of Thai swamp buffaloes received different vaccines and were labeled as 100 or 200 μg of the rOmpH with CpG-ODN2007, commercial HS bacterin vaccine, and nonvaccinated control groups. Sera and whole blood were collected to examine the antibody levels and cellular immune response using indirect ELISA and MTT assay, respectively. Challenge exposure was performed with virulent P. multocida strain M-1404 serotype B:2 on day 72 of the experiment. The antibody titers to P. multocida among immunized buffaloes were significantly higher than in the control group (p