Cellular vesicles-based "all-in-one" vaccine platform triggers mucosal immunity against respiratory viruses

Viruses transmitted through the respiratory tract tend to have short incubation periods and are highly contagious, thus being one of the main triggers of acute respiratory illnesses. Vaccines are important tools for reducing viral infections and preventing serious illness, hospitalization, and death. However, vaccines are still not widely accessible in some areas, particularly in low-income countries, because of limited production capacity and inadequate medical personnel, resulting in high morbidity and mortality rates during pandemics. Therefore, there is an urgent need for the development of vaccines that can be rapidly manufactured and self-administered in response to pandemics caused by respiratory-transmitted viruses. In this work, we developed an inhalable vaccine platform consisting of antigen-engineered cell membrane vesicles (CMVs) and cholesterolized CpG anchoring to the vesicle surface to establish an "all-in-one" vaccine platform (antigen/CpG-CMVs), which could induce mucosal immunity upon oropharyngeal inhalation to protect against viral infections in the respiratory tract. Its antigen, adjuvant, and particle size can be adjusted as needed through gene editing, cholesterol modification, and extrusion process, respectively. The lyophilized antigen/CpG-CMVs can be distributed without cold-chain transportation and can be self-administered by inhalation upon reconstitution. We found that this inhalable "all-in-one" vaccine induced not only systemic immunity but also mucosal immunity in the respiratory tract, as reflected by the enhanced levels of systemic immunoglobulin G (IgG) and respiratory secreted immunoglobulin A (sIgA). This work may validate engineered cell membrane vesicles as an inhalable vaccine platform and a promising avenue for future vaccine development to protect against pandemics.