AUTHOR=Zhang Zhihan , Yang Yumeng , Huang Liwen , Yuan Lei , Huang Sijian , Zeng Zihang , Cao Yuan , Wei Xianghong , Wang Xiaomei , Shi Mingsong , Zhong Maohua TITLE=Nanotechnology-driven advances in intranasal vaccine delivery systems against infectious diseases JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1573037 DOI=10.3389/fimmu.2025.1573037 ISSN=1664-3224 ABSTRACT=Outbreaks of emerging and re-emerging infectious diseases have consistently threatened human health. Since vaccinations are a powerful tool for preventing infectious illnesses, developing new vaccines is essential. Compared to traditional injectable vaccines, mucosal vaccines have the potential to offer more effective immune protection at mucosal sites. Mucosal immunization strategies include sublingual, oral, intranasal, genital, and rectal routes, in which intranasal immunization being the most efficient and applicable method for mucosal vaccine delivery. Nevertheless, low antigen availability and weak immunogenicity making it challenging to elicit a potent immune response when administered intranasally, necessitating the incorporation of immune delivery systems. However, there is a notable absence of reviews that summarize the intranasal vaccine delivery system against infectious disease. Therefore, this review summarizes the recent advances in intranasal delivery systems, classified by physical and chemical properties, and proposes potential improvement strategies for clinical translation. This review elucidates the potential and current status of intranasal delivery systems, while also serving as a reference point for the future development of intranasal vaccines.