Capsular glycan recognition provides antibody-mediated protection against tuberculosis
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ABSTRACT:
PROVIDER: PRJNA594355 | ENA |
REPOSITORIES: ENA
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Project description:Increasing evidence suggests that antibodies (Abs) can have protective roles in M. tuberculosis (Mtb) infection but knowledge of the most relevant protective antigens and epitopes in humans is limited. Using novel glycan arrays, we establish that human serum IgG induced against the M. tuberculosis (Mtb) capsular polysacharide arabinomannan (AM) in natural Mtb infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide (OS) motifs within AM and its functions between BCG vaccination and/or controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We show that anti-AM IgG from asymptomatic but not diseased individuals is protective, and provide data suggesting a role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our human 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.
2019-12-10 | GSE141679 | GEO
Project description: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.
| S-EPMC7108924 | biostudies-literature
Project description:N-glycans, which represent >50% mass of the HIV-1 envelope (Env) trimer, play important roles for virus-cell entry and immune evasion. How each glycan unit interacts to shape the Env protein-sugar complex and affects Env function is not well understood. Here, high-resolution glycomics analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation-site not only affected the Env structure at distant locations, but also had a ripple effect on Env-wide glycan processing, virus infectivity, and antibody recognition and virus neutralization. Specifically, the N262 glycan, although not located in the CD4-binding site, controlled Env binding to the CD4 receptor, affected the recognition of Env by several glycan-dependent broadly neutralizing antibodies, and altered heterogeneity of glycosylation at several sites, with N156, N160, and N448 displaying limited glycan processing. Molecular dynamic simulations visualized how specific oligosaccharide positions can move to compensate for loss of a glycan. This study demonstrates how changes in individual glycan units can alter molecular dynamics and processing of the Env-glycan shield and, consequently, Env function.
2021-09-09 | PXD017941 | Pride
Project description:The primary mechanism by which pneumococcal capsular polysaccharide-based vaccines are believed to mediate protection is by induction of serotype-specific opsonic antibodies that facilitate bacterial killing by phagocytes (opsonophagocytosis). However, antibodies that are protective against experimental pneumococcal pneumonia in mice but do not promote opsonophagocytic killing in vitro have also been identified 1-3. Such non-opsonic antibodies are associated with bacterial clearance in vivo, but the mechanism by which this occurs is unknown. In this letter, we demonstrate that a protective, non-opsonic serotype 3 pneumococcal capsular polysaccharide-specific monoclonal antibody (MAb) enhances quorum sensing, which results in competence induction and fratricide of serotype 3 pneumococcus. Gene expression profile analysis revealed that the MAb together with the pneumococcal autoinducer, competence stimulating peptide 2 (CSP2), augments differential expression of competence (com) related bacteriocin-like peptide (blp) genes that are known to be involved in pneumococcal fratricide. Taken together, these findings reveal a previously unsuspected mechanism of antibody action, namely, enhancement of quorum sensing and bacterial fratricide. Given that this activity does not require phagocytes, antibodies that function accordingly may hold promise as adjuncts to current vaccines or as desired products of next generation pneumococcal vaccines. 6 samples
2011-03-01 | E-GEOD-27258 | biostudies-arrayexpress
Project description:The primary mechanism by which pneumococcal capsular polysaccharide-based vaccines are believed to mediate protection is by induction of serotype-specific opsonic antibodies that facilitate bacterial killing by phagocytes (opsonophagocytosis). However, antibodies that are protective against experimental pneumococcal pneumonia in mice but do not promote opsonophagocytic killing in vitro have also been identified 1-3. Such non-opsonic antibodies are associated with bacterial clearance in vivo, but the mechanism by which this occurs is unknown. In this letter, we demonstrate that a protective, non-opsonic serotype 3 pneumococcal capsular polysaccharide-specific monoclonal antibody (MAb) enhances quorum sensing, which results in competence induction and fratricide of serotype 3 pneumococcus. Gene expression profile analysis revealed that the MAb together with the pneumococcal autoinducer, competence stimulating peptide 2 (CSP2), augments differential expression of competence (com) related bacteriocin-like peptide (blp) genes that are known to be involved in pneumococcal fratricide. Taken together, these findings reveal a previously unsuspected mechanism of antibody action, namely, enhancement of quorum sensing and bacterial fratricide. Given that this activity does not require phagocytes, antibodies that function accordingly may hold promise as adjuncts to current vaccines or as desired products of next generation pneumococcal vaccines.
2011-03-01 | GSE27258 | GEO
Project description:A glycan-based adjuvant expands the breadth and duration of protection of mRNA-based vaccines.
| PRJNA1395636 | ENA
Project description:Identification of a potent V3 glycan site broadly neutralizing antibody targeting an N332gp120 glycan-independent epitope
| PRJEB102776 | ENA
Project description:Identification of a potent V3 glycan site broadly neutralizing antibody targeting an N332gp120 glycan-independent epitope
| PRJEB102783 | ENA
Project description:Identification of a potent V3 glycan site broadly neutralizing antibody targeting an N332gp120 glycan-independent epitope
| PRJEB102777 | ENA
Project description:Dr. Lebrilla's lab is working on another set of transcriptomics experiments which will measure whether HMO (human milk oligosacharides) elicit a differential response on Caco2 in the presence of B.infantis. They wish to supplement the data obtained with the Illumina platform with glycan-related expression data obtained with the Gene-chips to achieve a more complete understanding on how Caco2 cells respond to the presence of HMOs and B.infantis. The transcriptomics data is being complemented by qPCR based bacterial-epithelial cells binding assays, and glycan arrays assays for which they have initiated a collaboration with the CFG Core H (David Smith).
2011-06-14 | GSE29934 | GEO