Intranasal vaccination of neonatal mice with polysaccharide conjugate vaccine for protection against pneumococcal otitis media

Abstract

Streptococcus pneumoniae is the leading bacterial cause of acute otitis media (OM) in young children, and can often produce invasive disease. Typical intramuscular routes of vaccination are poorly protective against development of OM. In the present study, we intranasally (i.n.) inoculated neonatal 1-week-old mice with pneumococcal polysaccharide conjugate vaccine using IL-12 as a mucosal adjuvant. The protective efficacy of this treatment was tested by challenging immunized infant (3-week-old) mice with bacteria to induce OM and invasive disease. i.n. vaccination was found to enhance levels of specific antibodies in middle ear (ME) washes and sera from wild-type (but not IFN-γ −/−) mice. Immunization in the presence of IL-12 resulted in enhanced clearance of S. pneumoniae from the ME. Opsonization of bacteria with ME wash fluids or sera from immunized mice caused increased bacterial clearance from the ME of naïve mice. In addition, immunized mice demonstrated 89% survival after OM-induced invasive pneumococcal infection, compared to 22% survival in unvaccinated mice. These results indicate that i.n. vaccination of neonatal mice in the presence of IL-12 is able to enhance IFN-γ dependent ME mucosal and systemic immune responses to pneumococci and efficiently protect against both OM and invasive infection.