Previous studies have demonstrated that nasal administration of the outer membrane protein of Porphyromonas gingivalis (40k-OMP) with cholera toxin (CT) as an adjuvant elicits protective immune responses against P. gingivalis in young mice. In the present study, we investigated whether administration of 40k-OMP plus CT would also induce 40k-OMP-specific antibody (Ab) responses to provide protective immunity against P. gingivalis infection in aged mice. Nasal immunization with 40k-OMP plus CT elicited 40k-OMP-specific IgG and IgA Ab responses in serum and a significant anti-40k-OMP IgA Ab response in nasal washes and saliva in 1- and 2-year-old mice. Furthermore, both Th1- and Th2-type cytokine responses were induced by the immunization, and cytokine-associated IgG1, IgG2a, and IgG2b Ab responses were observed in the spleens of aged mice. Although the aged mice showed lower 40k-OMP-specific Ab responses than young mice, their mucosal IgA Ab titers as well as serum IgG Ab responses indicated a retained ability to mediate protective immunity; the only exception was saliva in 2-year-old mice. These findings suggest that nasal immunization with 40k-OMP plus CT can be a potential vaccination strategy for eliciting levels of Abs sufficient to provide protective immunity against P. gingivalis infection in aged mice. (J Oral Sci 55, 107-114, 2013)