[Frontiers in Bioscience E4, 2638-2646, June 1, 2012]

Role of toll like receptors in the antibody response to encapsulated bacteria

John R. Schreiber1

1The Floating Hospital for Children at Tufts Medical Center and The Department of Pediatrics, Tufts University School of Medicine, Boston Massachusetts 02111, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The immune response to T cell independent bacterial polysaccharides
3.1. TNFR BAFF and APRIL required for humoral response to polysaccharides
3.2. Ontogeny of BAFF and APRIL receptors
4. Toll like receptors and B cell function and differentiation
4.1. TLR presence on B cells
4.2. TLR engagement augments BAFF and April mediated antibody secretion
5. The immune response to bacterial polysaccharide protein glycoconjugate vaccines
5.1. Conversion of the T cell independent response to T cell dependent reponse
5.2. Limitations of conjugate vaccines
6. Toll like receptor agonists are effective adjuvants for immunity to encapsulated bacteria
6.1. Role of TLR to immunity to intact encapsulated bacteria
6.2. TLR stimulation enhances the antibody response to pure bacterial PS
6.3. TLR agonists are effective adjuvants for bacterial PS glycoconjugate vaccines
6.4. TLR agonists stimulate humoral immunity to non-capsular protein antigens of encapsulated bacteria
7. Conclusions
8. References

1. ABSTRACT

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.