Emerging horizons in periodontal vaccine development: From concept to clinical translation (Review)

Periodontal disease is a multifactorial chronic inflammatory disease of tooth‑supporting tissues that initiates with a dysbiotic microbial biofilm and a dysregulated host immune response. Conventional treatment with mechanical debridement and antimicrobials is beneficial only in the short term and does not address the underlying immune pathological process or prevent recurrence. Currently, one of the novel approaches for combating periodontal disease involves preventive and therapeutic strategies, by modulating the host immune system in order to safeguard them over a prolonged period of time from periodontal infection caused by Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola and Prevotella intermedia, is the utilization of periodontal vaccines. Recent advances in reverse vaccinology, epitope prediction using artificial intelligence, lipid nanoparticle delivery systems and messenger RNA vaccines as a delivery platform have facilitated periodontal vaccine development. Several immunogenic responses have been demonstrated in animal studies and early human trials, such as blocking adherence and colonization with neutralizing antibodies. There are, however, challenges, such as antigenic variability, potential cross‑reactivity with host tissues and the need for safe and sustained immune activation in the oral setting. However, recent advances in areas, such as molecular biology, immunogen design, bioinformatic approaches, mucosal adjuvant systems and nanoparticle‑based delivery technologies may render these confounders obsolete. The present review aimed to present a comprehensive and integrated overview of periodontal vaccine development that merges classic vaccine development methods with emerging technologies, as well as translation challenges and clinical perspectives. Periodontal vaccines may provide immunological protection against periodontal disease, support a paradigm shift away from mechanical plaque control, and offer long‑term, host‑modulated protection.