Intranasal immunization with pneumococcal polysaccharide conjugate vaccines protects mice against invasive pneumococcal infections

Host defenses against Streptococcus pneumoniae depend largely on opsonophag ocytosis mediated by antibodies and complement. Since pneumococcus is a res piratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effectiv e adjuvants are required. Protein antigens induce significant mucosal immun oglobulin A(IgA) and systemic IgG responses when administered intranasally (i.n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumoc occal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was stud ied in mice after i.n. immunization with RV. Antibodies were measured in se rum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers in duced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, fo r serotype 1, serum IgG titers were comparable to titers induced by subcuta neous immunization. In addition, i.n. immunization with PNC-1 in RV elicite d detectable mucosal IgA. These results demonstrate that RV is a potent muc osal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and prot ection correlated significantly with the serum IgG titers. Similarly, the s urvival of mice immunized i.n. with PNC-3 in RV was significantly prolonged . These results indicate that mucosal vaccination with PNC and adjuvants ma y be an alternative strategy for prevention against pneumococcal infections .