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Rapid synthesis and immunogenicity of mycobacterial (1→5)-α-d-arabinofuranan

Leelayuwapan, Haris, Ruchirawat, Somsak, Boonyarattanakalin, Siwarutt
Carbohydrate polymers 2019 v.206 pp. 262-272
Mycobacterium tuberculosis, adjuvants, arabinans, immune response, immunogenicity, in vivo studies, inflammation, innate immunity, interferon-gamma, interleukin-12, interleukin-2, macrophages, mice, polymerization, tetanus, tumor necrosis factor-alpha
A rapid synthesis of the α(1→5) arabinofuranan polysaccharides, found on the outer surface of Mycobacterium tuberculosis (Mtb), is achieved by a regio- and stereocontrolled ring opening polymerization of β-d-arabinofuranose-1,2,5-orthobenzoate. The robust polymerization reaction allows the incorporation of an amine linker, which was used to conjugate with protein tetanus toxoid (TT) to further investigate its adjuvant activities. The synthetic arabinan, which is the glycan on the non-reducing end of Mtb lipoarabinomannan (LAM), was evaluated for its immunological properties in vitro and in vivo. Systemic inflammation and the promotion of innate immune response were observed in macrophages treated with the synthetic arabinan as an adjuvant through an increase in the production of TNF-α and IL-12. In vivo evaluation of IFN-γ, IL-2, and TNF-α productions in mice pre-immunized with the synthetic arabinan conjugated TT indicated great enhancements of the immunological responses when compared to that of TT alone.