Capsular glycan recognition provides antibody-mediated immunity against tuberculosis

• Published in: The Journal of clinical investigation Vol. 130; no. 4; pp. 1808 - 1822
• Main Authors: Chen, Tingting, Blanc, Caroline, Liu, Yanyan, Ishida, Elise, Singer, Sarah, Xu, Jiayong, Joe, Maju, Jenny-Avital, Elizabeth R, Chan, John, Lowary, Todd L, Achkar, Jacqueline M
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.04.2020
• Subjects: Analysis; Animals; Antibodies; Antibodies, Bacterial - immunology; Antigenic determinants; Antigens; Arabinomannan; BCG; BCG Vaccine - immunology; Biomedical research; Capsular polysaccharides; Cell-mediated immunity; Diseases; Epitopes; Female; Health aspects; HIV; Human immunodeficiency virus; Humans; Immigrants; Immunoglobulin G; Immunoglobulin G - immunology; Immunotherapy; Infections; Male; Mannans - immunology; Mice; Mycobacterium tuberculosis - immunology; Novels; Oligosaccharides; Oligosaccharides - immunology; Pathogens; Polysaccharides; Scientific equipment industry; THP-1 Cells; Tuberculosis; Tuberculosis - immunology; Tuberculosis vaccines; Vaccination; Vaccine development; Vaccines; Canada; United States; United States > US; Infectious disease; Immunoglobulins; Adaptive immunity; Immunology; Tuberculosis
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci128459

A better understanding of all immune components involved in protecting against Mycobacterium tuberculosis infection is urgently needed to inform strategies for novel immunotherapy and tuberculosis (TB) vaccine development. Although cell-mediated immunity is critical, increasing evidence supports that antibodies also have a protective role against TB. Yet knowledge of protective antigens is limited. Analyzing sera from 97 US immigrants at various stages of M. tuberculosis infection, we showed protective in vitro and in vivo efficacy of polyclonal IgG against the M. tuberculosis capsular polysaccharide arabinomannan (AM). Using recently developed glycan arrays, we established that anti-AM IgG induced in natural infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide motifs within AM and its functions in bacillus Calmette-Guérin vaccination and/or in controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We showed that anti-AM IgG from asymptomatic but not from diseased individuals was protective and provided data suggesting a potential role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.