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.
Highlights
The relevance of antibodies (Abs) in the defense against Mycobacterium tuberculosis infection remains uncertain
We have further demonstrated that Ab responses to capsular AM and the related cell wall glycolipid lipoarabinomannan (LAM) correlate strongly and significantly in patients with tuberculosis [10], suggesting, in accordance with other studies [12], that AM is the immunogenic portion of LAM
Participants were recruited under a protocol approved by the Oxfordshire Research Ethics Committee [18], and peripheral blood mononuclear cells (PBMCs) from independent healthy bacillus Calmette-Guerin (BCG) vaccinated subjects were collected under a protocol approved by the Institutional Review Board of the Albert Einstein College of Medicine
Summary
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. Sera were obtained from 30 healthy, M. tuberculosis–uninfected adults before and after (weeks 4, 8, and 24) primary or secondary BCG vaccination at the University of Oxford (Oxford, United Kingdom) [18]. Participants were recruited under a protocol approved by the Oxfordshire Research Ethics Committee [18], and peripheral blood mononuclear cells (PBMCs) from independent healthy BCG vaccinated subjects were collected under a protocol approved by the Institutional Review Board of the Albert Einstein College of Medicine. Capsular AM from BCG (Pasteur) or M. tuberculosis (H37Rv) was isolated, purified, and lyophilized as described [19]. LAM, isolated from the cell wall of M. tuberculosis H37Rv, was obtained from BEI Resources (NR-14848). Maxisorp plates were coated with AM or LAM at 10 μg/mL, sera were added at 1:50 dilution, and ELISAs were performed as described elsewhere [10], with further details in the Supplementary Methods
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