Role of Toll like receptors in the antibody response to encapsulated bacteria.

Encapsulated bacteria are major pathogens in humans. The capsular polysaccharides (PS) of these bacteria are T-independent type 2 antigens, are not processed by antigen presenting cells and do not induce T cell help. PS antigens are poor immunogens in children less than two years, the peak age incidence of encapsulated bacterial infection. The TNF family receptors BAFFR and TACI interaction with the cytokines BAFF and APRIL are essential co-stimulatory factors for humoral responses to PS. Linkage of PS to a carrier protein to make glycoconjugate vaccines, enhances the immune response to PS similar to a T cell dependent antigen. Multiple doses of glycoconjugate vaccines are required to elicit protection, making their use in the developing world problematic. TLR engagement augments BAFF mediated PS antibody responses and TLR ligands serve as adjuvants for induction of anti-PS antibodies either for pure PS or for PS-protein conjugate vaccines. A variety of TLR ligands stimulate increased production of antibodies directed to both PS and protein components of encapsulated bacteria, and glycoconjugate vaccines, suggesting their future role in immunization strategies.