Establishment of a novel adjuvant screening system for the development of intranasal vaccine adjuvants.

Vaccine adjuvants play a pivotal role in enhancing the immunogenicity of vaccines. Some vaccine modalities, such as subunit vaccines and split vaccines, are inherently poorly immunogenic and benefit greatly from combination with adjuvants. Notable examples, such as the herpes zoster glycoprotein E subunit vaccine and the Novavax COVID-19 (NVX-CoV2373) vaccine, underscore the importance of adjuvants in vaccination. Mucosal vaccines, and intranasal vaccines in particular, are gaining increasing attention for their potential to combat respiratory viral infections more effectively than subcutaneous and intramuscular vaccines. This is because mucosal vaccines can induce immunoglobulin (Ig)A production at mucosal surfaces to prevent the transmission of respiratory viruses such as influenza and severe acute respiratory syndrome coronavirus 2. However, few adjuvanted mucosal vaccines have been approved to date. To address this gap, we developed an adjuvant screening system to identify adjuvants suitable for use in combination with intranasal vaccines from a list of existing approved drugs or pharmaceutical additives. By analyzing biomarker gene expression levels, our screening system was able to predict the adjuvanticity and toxicity of a given adjuvant candidate in a short time. Using this screening system, we have to date identified some pharmaceutical additives, which induced a robust antigen-specific IgA antibody response following a single intranasal administration, without significant leukopenic toxicity or type I interferon inducibility. In this review, we discuss the development of our novel adjuvant evaluation system and its potential to enhance the efficacy of mucosal vaccines.