A mechanism for glycoconjugate vaccine activation of the adaptive immune system and its implications for vaccine design
A mechanism for glycoconjugate vaccine activation of the adaptive immune system and its implications for vaccine design
Avci FY et al. Nat. Med. 2011;17: 1602-9.
Speaker: Nai-Chi Yeh (葉乃綺) Time: 15:00~16:00, Feb. 29, 2012
Commentator: Dr. Yee-Shin Lin (林以行教授) Place: Room 601
Abstract
Capsular polysaccharides (CPSs), coating the bacterial surface, fail to induce CPSs-specific IgM-to-IgG switching and sustain T cell memory. However, when CPS conjugated with carrier proteins, it becomes a powerful immunogen. Thus, this technique of glycoconjugate has been used as vaccines to prevent infectious diseases causing by H. influenzae, S. pneumonia, and N. meningitides. Although conjugate vaccines are successfully applied in clinical settings, the mechanism of immune system responds to conjugate vaccine remains unclear. In this study, the authors investigated the cellular mechanisms of the immune response to glycoconjugate vaccines. First, they found that the molecule of type III polysaccharide of group B Streptococcus (GBSIII) coupled to a carrier protein could be taken up by B cells, processed into smaller glycans in endolysosomes, and then presented by MHC class II (MHCII) on the surface of antigen-presenting cells, but unconjugated GBSIII could not be presented. Furthermore, mice were primed with ovalbumin-GBSIII (GBSIII-OVA) and boosted by GBSIII conjugated with ovalbumin or tetanus toxoid. The two groups induced GBSIII-specific IgG, suggesting the recruitment of T cell help via carbohydrate recognition. The glycolconjugate could, but GBSIII could not induce memory. The CD4‑expressing T cells from the GBSIII-OVA-immunized mice specifically recognized the GBSIII in the context of MHCII, and interleukin (IL)‑2 and IL‑4 secreted from T cells could also help B cells to produce antibody. Finally, they found that mice immunized with GBSIII covalently linked to OVA peptide induced a significantly stronger humoral immune response, and the GBSIII-specific IgG also conferred greater protection than the mice immunized with GBSIII-OVA. Taken together, this study identifies the immune mechanisms that are involved in glycoconjugate immunization and provides a rational design of new vaccines against emerging bacterial infectious diseases.
References
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