Abstract: Respiratory infections remain a common global health problem. Particularly, the coronavirus disease 2019 (COVID-19)pandemic has posed a serious global health threat. Vaccination is a safe, effective and convenient way to prevent these infections, and respiratory mucosal vaccination could induce robust protective immune responses at the entry sites of pathogen infection. Based on the structure, organization and immune mechanisms of respiratory mucosa, and the challenges in the research and development of respiratory mucosal vaccines, with reference to the global experience in developing anti-COVID-19 vaccines in recent years, this review discusses the strategies to design effective respiratory mucosal vaccines using different adjuvants and delivery systems.