Polysaccharide (PS)-encapsulated bacteria such as Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococcus),
Neisseria meningitides (meningococcus) and group B streptococcus (GBS), cause a major proportion of disease in early childhood. Native PS
vaccines are immunogenic and provide protection against disease in healthy adults but do not induce immunological memory. PSs are T-cell-independent
antigens and do not elicit
antibodies in infants and young children, but by conjugating PS to
proteins they become T-cell dependent and immunogenic at an early age. Despite excellent efficacy of PS-
protein conjugate vaccines against invasive disease, protection against mucosal
infections such as pneumococcal
otitis media has been less efficacious. Circulating PS-specific
antibodies may protect against
infections at mucosal sites, but mucosal
immunoglobulin A antibodies may also contribute significantly to protection against mucosal
infections. Mucosal immunization of experimental animals with
conjugate vaccines against Hib, pneumococcus, meningococcus and GBS induces systemic and mucosal immune responses, which provide protection against carriage,
otitis media and invasive disease in a variety of challenge models, providing new means for protection against encapsulated bacteria. In addition, mucosal immunization of neonatal mice with a pneumococcal conjugate and the nontoxic adjuvant LT-K63 has been superior to parenteral immunization in eliciting protective
antibodies and PS-specific memory, and thus circumventing the limitations of antibody responses to PS that are responsible for enhanced susceptibility of neonates and infants to
infections caused by encapsulated bacteria. Through T-cell dependent enhanced immunogenicity of PS-
protein conjugate vaccines, mucosal immunization could be an attractive approach for early life immunization against encapsulated bacteria.