Engineering the supernatural: monoclonal antibodies for challenging infectious diseases

Grace, Patricia S.; Gunn, Bronwyn M.; Lu, Lenette L.

doi:10.1016/j.copbio.2022.102818

Cited by 5 publications

(3 citation statements)

References 87 publications

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“…Antibodies are leveraged in vaccines, diagnostics, and therapeutics in many infectious diseases but for tuberculosis (TB), their role is unclear (1)(2)(3)(4)(5). Unlike other pathogens, the presence of antibodies reactive to Mycobacterium tuberculosis (Mtb), the causative agent, is linked to neither protection nor disease (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…Antibodies function by the combination of the Fab domain binding to the antigen and Fc domain engaging receptors on immune cells to induce effector functions (2,5). Diversity within the Fc domain in subclass and post-translational glycosylation regulate binding to activating and inhibitory Fc receptors (FcRs) that initiate downstream signaling and immune cell activation (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Antigen specificity shapes antibody functions in tuberculosis

Miles,

Lu,

Bai

et al. 2024

Preprint

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Tuberculosis (TB) is the number one infectious disease cause of death worldwide in part due to an incomplete understanding of immunity. Emerging data highlight antibody functions as correlates of protection and disease across human TB. However, little is known about how antibody functions impactMycobacterium tuberculosis (Mtb), the causative agent. Here, we use antigen specificity to understand how antibodies mediate host-Mtbinteractions. We focus onMtbcell wall and ESAT-6 & CFP-10, critical bacterial structural and secreted virulence proteins. In polyclonal IgG from TB patients, we observe that antigen specificity alters IgG subclass and glycosylation that drives Fc receptor binding and effector functions. Through in vitro models ofMtbmacrophage infection we find thatMtbcell wall IgG3, sialic acid, and fucose increase opsonophagocytosis of extracellularMtband bacterial burden, suggesting that some polyclonal IgG enhance disease. In contrast, ESAT-6 & CFP-10 IgG1 inhibits intracellularMtb, suggesting that antibodies targeting secreted virulence factors are protective. We test this hypothesis by generating a mAb that reacts to ESAT-6 & CFP-10 and show that it alone inhibits intracellularMtb. Understanding which antigens elicit antibody mediated disease enhancement and or protection will be critical in appreciating the many roles for antibodies in TB.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antigen specificity shapes antibody functions in tuberculosis

Miles,

Lu,

Bai

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Monoclonal Abs (MAbs) are produced by single B-lymphocyte clones and have high specificity in targeting its corresponding antigen(s). They have been produced for the treatment of cancers, auto-immune and allergic diseases as well as infectious diseases [ 109 ] including COVID-19 [ 110 ]. Various MAbs have been produced against Aspergillus spp.…”

Section: Introductionmentioning

confidence: 99%

Humoral Immunity Against Aspergillus fumigatus

Dellière

Aimanianda

2023

Mycopathologia

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Aspergillus fumigatus is one the most ubiquitous airborne opportunistic human fungal pathogens. Understanding its interaction with host immune system, composed of cellular and humoral arm, is essential to explain the pathobiology of aspergillosis disease spectrum. While cellular immunity has been well studied, humoral immunity has been poorly acknowledge, although it plays a crucial role in bridging the fungus and immune cells. In this review, we have summarized available data on major players of humoral immunity against A. fumigatus and discussed how they may help to identify at-risk individuals, be used as diagnostic tools or promote alternative therapeutic strategies. Remaining challenges are highlighted and leads are given to guide future research to better grasp the complexity of humoral immune interaction with A. fumigatus.

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NIAID/SMB Workshop on Multiscale Modeling of Infectious and Immune-Mediated Diseases

Shabman,

Craig,

Laubenbacher

et al. 2024

Bull Math Biol

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On July 19th, 2023, the National Institute of Allergy and Infectious Diseases co-organized a workshop with the Society of Mathematical Biology, with the authors of this paper as the organizing committee. The workshop, “Bridging multiscale modeling and practical clinical applications in infectious diseases” sought to create an environment for mathematical modelers, statisticians, and infectious disease researchers and clinicians to exchange ideas and perspectives.

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Engineering the supernatural: monoclonal antibodies for challenging infectious diseases

Cited by 5 publications

References 87 publications

Antigen specificity shapes antibody functions in tuberculosis

Antigen specificity shapes antibody functions in tuberculosis

Humoral Immunity Against Aspergillus fumigatus

NIAID/SMB Workshop on Multiscale Modeling of Infectious and Immune-Mediated Diseases

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