Recombinant IgA Antibodies

Yoo, Esther M.; Chintalacharuvu, Koteswara R.; Morrison, Sherie L.

doi:10.1007/978-0-387-72232-0_15

Cited by 4 publications

(2 citation statements)

References 138 publications

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“… 29 , 33–35 However, due to the heavy and complex glycosylation of sIgA, systems that improve yield fail to produce the proper glycan patters, introducing immunogenicity concerns as well as significant differences in sIgA function. 34 , 36 , 37 Additional challenges include capture material selection and characterization of multimers and aggregates as recently reviewed. 38 The many difficulties in recombinant production of secretory IgA underscore the practical and translational value in extracting naturally occurring human milk IgA which is abundant, polyclonal, and primarily in the secretory IgA format.…”

Section: Discussionmentioning

confidence: 99%

In vivo antiviral efficacy of LCTG-002, a pooled, purified human milk secretory IgA product, against SARS-CoV-2 in a murine model of COVID-19

Mane,

Mehta,

Alvarez

et al. 2024

Human Vaccines & Immunotherapeutics

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Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosae, with secretory form (sIgA) being dominant and uniquely stable. sIgA is challenging to produce recombinantly but is naturally found in human milk, which could be considered a global resource for this biologic, justifying its development as a mucosal therapeutic. Presently, SARS-CoV-2 was utilized as a model mucosal pathogen, and methods were developed to efficiently extract human milk sIgA from donors who were naïve to SARS-CoV-2 or had recovered from infection that elicited high-titer anti-SARS-CoV-2 Spike sIgA in their milk (pooled to make LCTG-002). Mass spectrometry determined that proteins with a relative abundance of 1% or greater were all associated with sIgA. Western blot demonstrated that all batches consisted predominantly of sIgA. Compared to control IgA, LCTG-002 demonstrated significantly higher Spike binding (mean endpoint of 0.87 versus 5.87). LCTG-002 was capable of blocking the Spike receptor-binding domain – angiotensin-converting enzyme 2 (ACE2) interaction with significantly greater potency compared to control (mean LCTG-002 IC50 154ug/mL versus 50% inhibition not achieved for control), and exhibited significant neutralization activity against Spike-pseudotyped virus infection (mean LCTG-002 IC50 49.8ug/mL versus 114.5ug/mL for control). LCTG-002 was tested for its capacity to reduce viral lung burden in K18+hACE2 transgenic mice inoculated with SARS-CoV-2. LCTG-002 significantly reduced SARS-CoV-2 titers compared to control when administered at 0.25 mg/day or 1 mg/day, with a maximum TCID50 reduction of 4.9 logs. This innovative study demonstrates that LCTG-002 is highly pure and efficacious in vivo, supporting further development of milk-derived, polyclonal sIgA therapeutics.

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Section: Discussionmentioning

confidence: 99%

In vivo antiviral efficacy of LCTG-002, a pooled, purified human milk secretory IgA product, against SARS-CoV-2 in a murine model of COVID-19

Mane,

Mehta,

Alvarez

et al. 2024

Human Vaccines & Immunotherapeutics

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“…Although IgA replacement therapy has been attempted in humans, this approach has been variably effective because not all of these replacement products contained sIgA, and IgA is normally transported from sites of local production (and not the blood stream) to the mucosa [ 90 , 92 , 93 , 94 , 95 , 96 , 97 ]. However, there continue to be incremental, albeit critical, advances in IgA biology relating to glyco-engineering, as well as recombinant DNA expression methodologies that raise the possibility of sIgA replacement therapy becoming part of the standard of care for B cell IEI patients in the future [ 91 , 98 , 99 , 100 ]. Some of the scientific bottlenecks in this regard, for which solutions are being actively pursued, include extending the half-life of IgA by engineering its association with the neonatal Fc receptor and addressing the feasibility of commercial scale production by generating sIgA in various eukaryotic expression systems, including plants, for oral consumption by humans [ 91 , 98 , 100 ].…”

Section: The Futurementioning

confidence: 99%

Clinical Aspects of B Cell Immunodeficiencies: The Past, the Present and the Future

Ahmed

Lippner

Khanolkar

2022

Cells

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B cells and antibodies are indispensable for host immunity. Our understanding of the mechanistic processes that underpin how B cells operate has left an indelible mark on the field of clinical pathology, and recently has also dramatically reshaped the therapeutic landscape of diseases that were once considered incurable. Evaluating patients with primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) that primarily affect B cells, offers us an opportunity to further our understanding of how B cells develop, mature, function and, in certain instances, cause further disease. In this review we provide a brief compendium of IEI that principally affect B cells at defined stages of their developmental pathway, and also attempt to offer some educated viewpoints on how the management of these disorders could evolve over the years.

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Mucosal Immune Defense

Kaetzel¹

Encyclopedic Reference of Cancer

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Recombinant IgA Antibodies

Cited by 4 publications

References 138 publications

In vivo antiviral efficacy of LCTG-002, a pooled, purified human milk secretory IgA product, against SARS-CoV-2 in a murine model of COVID-19

In vivo antiviral efficacy of LCTG-002, a pooled, purified human milk secretory IgA product, against SARS-CoV-2 in a murine model of COVID-19

Clinical Aspects of B Cell Immunodeficiencies: The Past, the Present and the Future

Mucosal Immune Defense

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