Fc Receptors: Introduction

Hogarth, P. Mark

doi:10.1111/imr.12372

Cited by 13 publications

(7 citation statements)

References 30 publications

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“…Although these titers peaked at V2, they generally declined after additional vaccinations ( Figure 1D). Because the Fc fragment of different IgG-specific subclasses have varying affinity for cellular Fc receptors on effector cells [36][37][38], we next determined whether the induction of multiple Fc-mediated effector functions (eg, ADMP/ADNP, cytokine expression, activation of NK cells) correlated with an EBOV-GP IgG-specific subclass. To determine whether total IgG or an IgG subclass was associated with a specific function, Spearman coefficients were used to determine correlation.…”

Section: Specific Activitymentioning

confidence: 99%

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Luke

Bennett

Gerhardt

et al. 2018

The Journal of Infectious Diseases

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Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-α-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.

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Section: Specific Activitymentioning

confidence: 99%

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Luke

Bennett

Gerhardt

et al. 2018

The Journal of Infectious Diseases

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“…To be suitable for cysteine mutagenesis, the sites need to be in a region of the Fc that, when mutated to cysteine would not destabilize the structure of the antibody or interfere with FcRn binding in order to maintain an IgG-like half-life when conjugated. We were also interested in generating antibody variants with diminished Fc effector functions and focused on amino acids located at the binding interfaces between the Fc and FcγRs [29]. Moreover, to be compatible for cysteine mutagenesis, the sites need be solvent exposed and, when mutated, maintain the proper folding and structure of the antibody.…”

Section: Selection Of Cysteine Conjugation Sites In the Fc Domain Of mentioning

confidence: 99%

“…A potential dose-limiting toxicity of ADCs can be caused by exposure of the cytotoxic agent to non-tumor cells through engagement of the IgG Fc with FcRs [29,34]. We hypothesized that a strategy to limit potential FcRs-mediated toxicities of ADC would be to diminish FcR binding of the ADC by introducing mutations that abolish the interaction between the ADC with the FcRs.…”

Section: Binding Of Antibodies and Adcs To Human Fcrsmentioning

confidence: 99%

Rational design, biophysical and biological characterization of site-specific antibody-tubulysin conjugates with improved stability, efficacy and pharmacokinetics

Thompson¹,

Fleming²,

Bezabeh³

et al. 2016

Journal of Controlled Release

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“…Less obviously but becoming more clear, FcR and Fc allotypes may confound otherwise simple antibody transfer experiments, and the picture becomes far more complicated when antibody glycosylation is taken into account. Many of the complications and cautions, still unfolding, are reviewed in a recent volume (Hogarth 2015 ).…”

Section: A Note Of Caution On Species and Allelic Differencesmentioning

confidence: 99%

Cell-targeting antibodies in immunity to Ebola

Schmaljohn

Lewis

2016

Pathogens and Disease

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As the 2014–15 Ebola virus epidemic in West Africa evolved from emergency to lesson, developers of both vaccines and therapeutic antibodies were left with the puzzlement of what kinds of anti-Ebola antibodies are predictably desirable in treating the afflicted, and what antibodies might account for the specific and lasting protection elicited by the more effective vaccines. The facile answer in virology is that neutralizing antibody (NAb) is desired and required. However, with Ebola and other filoviruses (as with many prior viral examples), there are multiple discordances in which neutralizing antibodies fail to protect animals, and others in which antibody-mediated protection is observed in the absence of measured virus neutralization. Explanation presumably resides in the protective role of antibodies that bind and functionally ‘target’ virus-infected cells, here called ‘cell-targeting antibody’, or CTAb. To be clear, many NAbs are also CTAbs, and in the case of Ebola the great majority of NAbs are likely CTAbs. Isotype, glycosylation, and other features of CTAbs are likely crucial in their capacity to mediate protection. Overall, results and analysis invite an increasingly complex view of antibody-mediated immunity to enveloped viruses.

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Fc Receptors: Introduction

Cited by 13 publications

References 30 publications

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Rational design, biophysical and biological characterization of site-specific antibody-tubulysin conjugates with improved stability, efficacy and pharmacokinetics

Cell-targeting antibodies in immunity to Ebola

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