NKT cell-dependent PspA-specific IgA production caused by mucosal administration of a novel nanoparticle pneumococcal vaccine.

Pneumonia is one of the leading causes of death worldwide, with Streptococcus pneumoniae being a major causative agent of community-acquired pneumonia. In immunocompromised infants and the elderly, this pathogen can invade the bloodstream and cerebrospinal fluid, leading to invasive pneumococcal diseases (IPDs), such as bacteremia and meningitis. Currently, vaccines targeting the capsular polysaccharides of pneumococcus are available to prevent pneumococcal infection. However, these vaccines have limitations, including incomplete coverage of all serotypes. Therefore, there is a need for next-generation vaccines that are independent of serotype variation. In this study, we developed a novel pneumococcal vaccine using pneumococcal surface protein A (PspA), a virulence factor presents on the surface of all pneumococcal strains, as the antigen. PspA was conjugated with iron oxide nanoparticles (IONPs), serving as both a carrier and a potential adjuvant. When administered intratracheally to mice, this vaccine, PspA-IONP, induced the formation of inducible bronchus-associated lymphoid tissue (iBALT) in the lungs and stimulated antibody production both systemically and on mucosal surfaces, thereby conferring resistance to pneumococcal infection. We focused on invariant natural killer T (iNKT) cells due to their role in antibody production by B cells. Notably, mucosal IgA antibodies induced by this vaccine were significantly reduced in iNKT cell-deficient (Jα18KO) mice compared to wild-type mice. The expression of pIgR, which is crucial for IgA secretion, as well as the production of several cytokines involved in pIgR expression and B cell activation, were also significantly decreased in Jα18KO mice. These results suggest that iNKT cells play a central role in promoting IgA secretion by directly or indirectly inducing multiple cytokines. PspA-IONP demonstrates potential as a novel vaccine platform that induces anti-pneumococcal immunity. Furthermore, this platform can be adapted to combat other respiratory infections by modifying the antigen conjugated to the IONPs.