The reduction of brain amyloid beta (Aβ) peptides by anti-Aβantibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβpeptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβantibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβantibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42compared to Aβfibrils. The levels of serum anti-Aβantibodies and plasma Aβpeptides increased in both animals and decreased the brain Aβ40level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβantibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβpeptides and their toxic effects via clearance of Aβpeptides by generated antibodies.