Periodontal disease is a highly prevalent disorder affecting up to 90% of the global population. Recent epidemiological studies have shown that an association exists between periodontal disease and cardiovascular disease. Porphyromonas gingivalis, the causative agent of destructive chronic inflammation in the periodontium, can accelerate atheroma deposition in animal models. Emerging evidence suggests that vaccination against this pathogen's virulence factors may confer disease resistance. In this review, we focus on the role of inflammatory mechanisms in the formation and activation of atherosclerotic plaques accelerated by P. gingivalis in an apo E-deficient mouse model. Further, we examine whether a nasal vaccine-induced antigen-specific mucosal response can reduce P. gingivalis-accelerated atherosclerosis.