Biomedical subjects

Julia Y Wang

Publications and source records attributed to Julia Y Wang.

5 recordsLinked to original sources

PubMed2003

Biological chemistry of immunomodulation by zwitterionic polysaccharides.

Capsular polysaccharides isolated from pathogenic bacteria are comprised typically of many repeating units from one to eight or more monosaccharides in length. These polysaccharides stimulate the murine humoral immune system to elicit primarily IgM antibody responses. Studies conducted primarily in the mouse have characterized these polymers as T cell-independent antigens. These mouse studies and the relatively poor immunogenicity of polysaccharides in human hosts have led to the design of vaccines by coupling these polysaccharides to protein carriers to stimulate a T cell-dependent response. However, a newly described class of bacterial polysaccharides has been characterized that have the ability to modulate the cellular immune system. They are structurally diverse, but all share a zwitterionic charge motif that allows them to directly interact with T cells and antigen-presenting cells to initiate an immunomodulatory T cell response. These polymers, termed zwitterionic polysaccharides (ZPSs), elicit T cell-derived chemokines and cytokines that influence the immune response governing at least one classic host response to bacterial infection: abscess formation. This review will describe the biological and structural aspects of ZPSs that convey these activities.

Amino Acid Motifs↗

PubMed2003

A dually active anthrax vaccine that confers protection against both bacilli and toxins.

Systemic anthrax is caused by unimpeded bacillar replication and toxin secretion. We developed a dually active anthrax vaccine (DAAV) that confers simultaneous protection against both bacilli and toxins. DAAV was constructed by conjugating capsular poly-gamma-d-glutamic acid (PGA) to protective antigen (PA), converting the weakly immunogenic PGA to a potent immunogen, and synergistically enhancing the humoral response to PA. PGA-specific antibodies bound to encapsulated bacilli and promoted the killing of bacilli by complement. PA-specific antibodies neutralized toxin activity and protected immunized mice against lethal challenge with anthrax toxin. Thus, DAAV combines both antibacterial and antitoxic components in a single vaccine against anthrax. DAAV introduces a vaccine design that may be widely applicable against infectious diseases and provides additional tools in medicine and biodefense.

Animals↗

PubMed2003

Construction of designer glycoconjugate vaccines with size-specific oligosaccharide antigens and site-controlled coupling.

Coupling of carbohydrate antigens to protein carriers is a typical approach to enhancing the immunogenicity of carbohydrate-based vaccines. Glycoconjugates with well-defined structures are needed for studies defining the structural variables that govern antibody responses. We report a chemical strategy for preparation of an array of glycoconjugates containing saccharides of desired molecular sizes by selective depolymerization of bacterial polysaccharides and chemically controlled site-specific coupling. As an example, we synthesized and evaluated an oligosaccharide-based vaccine against type III group B Streptococcus.

Animals↗

PubMed2002

A unique structural pattern shared by T-cell-activating and abscess-regulating zwitterionic polysaccharides.

In contrast to the conventional dogma that carbohydrates are poorly immunogenic T-cell-independent antigens, zwitterionic polysaccharides (ZPSs) can significantly stimulate T-cell proliferation and regulate abscess formation in bacterial infection. Despite their similar biological activities, ZPSs from various bacteria are greatly different in primary chemical compositions and building block linkages. To identify the common structural features that govern the peculiar immunologic activity of ZPSs, we have been determining three-dimensional structures of compositionally different ZPSs by NMR spectroscopy and molecular mechanics and dynamics calculations. We report here the conformation of type 1 capsular polysaccharide from the human pathogen Streptococcus pneumoniae (Sp1) to be a right-handed helix with repeated zwitterionically charged grooves. We also report the striking similarity between the structures of Sp1 and our previously determined PS A2 from Bacteroides fragilis. These results support our hypothesis that T-cell-activating ZPSs assume similar conformational and charge patterns that are recognized by specific receptors and that account for their common property as T-cell activators.

Abscess↗

PubMed2002

Glycosaminoglycans are a potential cause of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory disease of connective tissue with unknown etiology. We investigated whether aberrant immune responses to glycosaminoglycans (GAGs), a major component of joint cartilage, joint fluid, and other soft connective tissue, causes this disease. Here we show that injection of GAGs such as hyaluronic acid, heparin, and chondroitin sulfates A, B, and C induce arthritis, tendosynovitis, dermatitis, and other pathological conditions in mice. We developed a technique by staining tissue specimens with fluorochrome- or biotin-labeled GAGs to visualize the direct binding between cells and GAGs. We discovered that inflammatory infiltrates from the affected tissue are dominated by a distinct phenotype of GAG-binding cells, a significant portion of which are CD4(+) T cells. GAG-binding cells seem to be expanded in bone marrow of GAG-immunized mice. Furthermore, we identified GAG-binding cells in inflamed synovial tissue of human patients with RA. Our findings suggest that carbohydrate self-antigenic GAGs provoke autoimmune dysfunctions that involve the expansion of GAG-binding cells which migrate to anatomical sites rich in GAGs. These GAG-binding cells might, in turn, promote the inflammation and pathology seen both in our murine model and in human RA.

Animals↗