Association of Human Antibodies to Arabinomannan With Enhanced Mycobacterial Opsonophagocytosis and Intracellular Growth Reduction

Abstract

Background. The relevance of antibodies (Abs) in the defense against Mycobacterium tuberculosis infection remains uncertain. We investigated the role of Abs to the mycobacterial capsular polysaccharide arabinomannan (AM) and its oligosaccharide (OS) fragments in humans.Methods. Sera obtained from 29 healthy adults before and after primary or secondary bacillus Calmette-Guerin (BCG) vaccination were assessed for Ab responses to AM via enzyme-linked immunosorbent assays, and to AM OS epitopes via novel glycan microarrays. Effects of prevaccination and postvaccination sera on BCG phagocytosis and intracellular survival were assessed in human macrophages.Results. Immunoglobulin G (IgG) responses to AM increased significantly 4–8 weeks after vaccination (P < .01), and sera were able to opsonize BCG and M. tuberculosis grown in both the absence and the presence of detergent. Phagocytosis and intracellular growth inhibition were significantly enhanced when BCG was opsonized with postvaccination sera (P < .01), and these enhancements correlated significantly with IgG titers to AM (P < .05), particularly with reactivity to 3 AM OS epitopes (P < .05). Furthermore, increased phagolysosomal fusion was observed with postvaccination sera.Conclusions. Our results provide further evidence for a role of Ab-mediated immunity to tuberculosis and suggest that IgG to AM, especially to some of its OS epitopes, could contribute to the defense against mycobacterial infection in humans.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

“…Recent reports suggest that antimycobacterial antibodies may act by increasing the rate of opsonophagocytosis and phagolysosomal fusion in infected macrophages (27). Nonetheless, efficacy for antibody from our protective donors required intact T-cell immunity (Fig.…”

“…However, the murine protection assay is both costly and cumbersome and requires a large amount of antibody. In vitro assays using macrophage-mediated killing might identify some protective antibodies (20,24,27), but given the dependence of T-cell immunity for full protection of the antibodies identified by our studies, they may not identify all donors making protective antibodies. We wanted to determine whether the WBA could be used to identify donors who make antibodies that are also protective in the murine assay.…”

“…Some recent studies have suggested that Mtb-specific antibodies may enhance phagocytosis of mycobacteria by macrophages (27). We, therefore, tested whether addition of antibodies from some of the HCWs enhanced mycobacterial phagocytosis.…”

Humoral immune response to Mycobactrium tuberculosis cell wall fraction and lipoarabinomannan antigens in Bangladeshi patients with active tuberculosis

“…Similar higher IgG antibody response to LAM has been found in patients with TB and is being used as a marker for serodiagnosis of TB [4][5][6][7]9]. Significant IgG response to arabinomannan has been found following BCG vaccination indicating its role in defense against mycobacterial infection [10].…”

Antibody-Based Immunotherapy To Treat and Prevent Infection with Hypervirulent Klebsiella pneumoniae

“…Polysaccharide capsules of diverse microbes elicit protective immune responses in the host (21,22). Clinical data from patients with recurrent hvKp-mediated liver abscesses indicate that opsonizing and killing efficacy of serum increases over time, consistent with an evolving protective antibody response (23).…”