The mucosal immune system of the upper respiratory tract and recent progress in mucosal vaccines

Abstract

The mucosal immune system prevents microorganism invasion through mucosal surfaces and consists of inductive and effector sites. Nasopharynx-associated lymphoid tissue (NALT) functions as an inductive site, inducing mucosal immune responses in the upper respiratory tract. It follows that intranasal vaccines may prevent upper respiratory infections. To induce and enhance the immune response by administering inactivated antigens intranasally, mucosal adjuvants have been developed, including mutant cholera toxin and cationic cholesteryl pullulan nanogel, which do not accumulate in the central nervous system. Moreover, multivalent pneumococcal polysaccharide conjugate vaccines are used to prevent invasive pneumococcal infections and otitis media, although they only provide moderate protection against acute otitis media because non-vaccine serotypes of Streptococcus pneumoniae and Haemophilus influenzae also cause this infection. To address this problem, pneumococcal surface protein A of S. pneumoniae and P6 of H. influenzae are used as broad-spectrum vaccine antigens. Alternatively, phosphorylcholine (PC) is present in the cell walls of both gram-positive and gram-negative bacteria and induces immune responses through antigenic activity. The significant effects of PC as a mucosal vaccine have been demonstrated through intranasal and sublingual immunization in mice. Furthermore, intranasal administration of PC reverses increases in IgE levels and prevents allergic rhinitis. After immunization with pneumococcal polysaccharide conjugate vaccine, intranasal immunization with PC boosts immune responses to vaccine strains and to PC itself. Thus, PC may be useful as a mucosal vaccine to prevent upper respiratory infections and allergic rhinitis, and it could be used as a booster to the currently used pneumococcal vaccine as it protects against non-vaccine strains.