Synthesis and immunogenicity of the Mycobacterium tuberculosis arabinomannan–CRM197 conjugate

Abstract

Lipoarabinomannan (LAM) is a major structural surface component of Mycobacterium tuberculosis. This study describes the synthesis of the well-defined lipoarabinomannan (LAM) specific dodecasaccharide–protein conjugate and immunological studies. Arabinomannan (AM) dodecasaccharide has been efficiently synthesized and covalently conjugated to carrier proteins, including cross reactive mutant (CRM197) diphtheria toxoid and bovine serum albumin (BSA) for novel neoglycoconjugates, creating a potent T-dependent conjugate vaccine. Preliminary mice immunization studies on the neoglycoconjugate revealed that it could give rise to a strong IgG antibody titer in mice at 4.0 μg dose with an aluminum phosphate adjuvant. AM–CRM197 shows potential as an excellent candidate for a new carbohydrate-based vaccine that would be capable of eliciting a protective immune response against tuberculosis.