Silver nanoparticle-adjuvanted vaccine protects against lethal influenza infection through inducing BALT and IgA-mediated mucosal immunity

Abstract Most of current influenza virus vaccines fail to develop a strong immunity at lung mucosae (site of viral entry) due to sub-optimal vaccination protocols ( e.g. inactivated virus administered by parenteral injections). Mucosal immunity could be improved by using locally-delivered vaccines containing appropriate adjuvants. Here we show, in a mouse model, that inclusion of silver nanoparticles (AgNPs) in virus-inactivated flu vaccine resulted in reduction of viral loads and prevention of excessive lung inflammation following influenza infection. Concomitantly, AgNPs enhanced specific IgA secreting plasma cells and antibodies titers, a hallmark of successful mucosal immunity. Moreover, vaccination in the presence of AgNPs but not with gold nanoparticles, protected mice from lethal flu. Compared with other commercial adjuvants (squalene/oil-based emulsion) or silver salts, AgNPs stimulated stronger antigen specific IgA production with lower toxicity by promoting bronchus-associated lymphoid tissue (BALT) neogenesis, and acted as a bona fide mucosal adjuvant.