Engineering tetravalent IgGs with enhanced agglutination potencies for trapping vigorously motile sperm in mucin matrix

Shrestha, Bhawana; Schaefer, Antje; Chavez, Elizabeth C.; Kopp, Alexander; Jacobs, Timothy M.; Moench, Thomas R.; Lai, Samuel K.

doi:10.1016/j.actbio.2020.09.020

Cited by 5 publications

(2 citation statements)

References 52 publications

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“…[ 19 ] Different mAbs and RSV were added to AM in a custom‐made small‐volume glass chamber, gently mixed, and sealed. [ 75 ] The samples were then incubated for ≈15 min at 37°C prior to microscopy. Particle motion was recorded using an EMCCD camera (Evolve 512; Photometrics, Tuscon, AZ) mounted on an inverted microscope (AxioObeserver D1; Zeiss, Thornwood, NY) equipped with an Alpha Plan‐Apo 100x/1.46 NA objective, environmental (temperature and CO2) control chamber and an LED light source (Lumencor Light Engine DAPI/GFP/543/623/690).…”

Section: Methodsmentioning

confidence: 99%

Inhaled “Muco‐Trapping” Monoclonal Antibody Effectively Treats Established Respiratory Syncytial Virus (RSV) Infections

McSweeney,

Alnajjar,

Schaefer

et al. 2024

Advanced Science

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Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable “muco‐trapping” variant of motavizumab (Mota‐MT), a potent neutralizing mAb against RSV F is engineered. Mota‐MT traps RSV in AM via polyvalent Fc‐mucin bonds, reducing the fraction of fast‐moving RSV particles in both fresh pediatric and adult AM by ≈20–30‐fold in a Fc‐glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota‐MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota‐MT to RSV‐infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000‐fold and 100 000‐fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota‐MT‐treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco‐trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections.

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Section: Methodsmentioning

confidence: 99%

Inhaled “Muco‐Trapping” Monoclonal Antibody Effectively Treats Established Respiratory Syncytial Virus (RSV) Infections

McSweeney,

Alnajjar,

Schaefer

et al. 2024

Advanced Science

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“…Shrestha and colleagues demonstrated that multivalent IgGs had enhanced sperm agglutinating activity in a mucin matrix designed to mimic human cervix environment. 83 Others have opted to engineer camelid-derived single-chain antibodies carrying IgA Fc regions, with great success. 19,72 In summary, the prospect of oral antibody prophylaxis, especially with SIgA, is of great interest as an adjunct to vaccination or antibiotic treatment.…”

Section: Summary and Perspectivesmentioning

confidence: 99%

The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections

Richards

Baranova

Mantis

2021

Human Vaccines & Immunotherapeutics

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Eliminating diarrheal diseases as a leading cause of childhood morbidity and mortality in low-and middleincome countries (LMICs) will require multiple intervention strategies. In this review, we spotlight a series of preclinical studies investigating the potential of orally administered monoclonal secretory IgA (SIgA) antibodies (MAbs) to reduce disease associated with three enteric bacterial pathogens: Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), and invasive Salmonella enterica serovar Typhimurium. IgA MAbs targeting bacterial surface antigens (flagella, adhesins, and lipopolysaccharide) were generated from mice, humanized mice, and human tonsillar B cells. Recombinant SIgA1 and/or SIgA2 derivates of those MAbs were purified from supernatants following transient transfection of 293 cells with plasmids encoding antibody heavy and light chains, J-chain, and secretory component (SC). When administered to mice by gavage immediately prior to (or admixed with) the bacterial challenge, SIgA MAbs reduced infection C. jejuni, ETEC, and S. Typhimurium infections. Fv-matched IgG1 MAbs by comparison were largely ineffective against C. jejuni and S. Typhimurium under the same conditions, although they were partially effective against ETEC. While these findings highlight future applications of orally administered SIgA, the studies also underscored the fundamental challenges associated with using MAbs as prophylactic tools against enteric bacterial diseases.

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Advances in long-acting injectables, implants, and vaginal rings for contraception and HIV prevention

Krovi

Johnson

Luecke

et al. 2021

Advanced Drug Delivery Reviews

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Engineering tetravalent IgGs with enhanced agglutination potencies for trapping vigorously motile sperm in mucin matrix

Cited by 5 publications

References 52 publications

Inhaled “Muco‐Trapping” Monoclonal Antibody Effectively Treats Established Respiratory Syncytial Virus (RSV) Infections

Inhaled “Muco‐Trapping” Monoclonal Antibody Effectively Treats Established Respiratory Syncytial Virus (RSV) Infections

The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections

Advances in long-acting injectables, implants, and vaginal rings for contraception and HIV prevention

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