Design and Evaluation of An Intranasal Carbohydrate-based Vaccine against Streptococcus pneumoniae Serotype 12F

Diseases caused by S. pneumoniae are the leading cause of child mortality, estimated to kill 1,000,000 children yearly. As antibiotic resistance of S. pneumoniae is rising, vaccination programs remain the most recommended solution. However, the existing pneumococcal polysaccharides vaccine (PPSV) proved only to induce T-independent immunity, and cold chain dependence of the protein conjugate vaccine (PCV) impedes its promotion in developing countries, where infections are most problematic. Affordable and efficient vaccines against pneumococcus are therefore in high demand. Here, we present an innovative intranasal vaccine Lipo⁺CPS12F&αGC, containing the capsular polysaccharides of S. pneumoniae 12F and the iNKT agonist α-galactosylceramide in cationic liposomes. The vaccine effectively activated iNKTs and promoted B cell maturation, stimulated the production of affinity-matured IgA and IgG in both the respiratory tract and systemic blood, and displayed sufficient protection efficacy both in vivo and in vitro. The novel vaccine is a promising cost-effective solution against pneumococcus, which can potentially be applied to other carbohydrate antigens covering more serotypes and pathogens.