Inhaled "Muco-Trapping" Monoclonal Antibody Effectively Treats Established Respiratory Syncytial Virus (RSV) Infections.

Autor: McSweeney MD; Inhalon Biopharma, Research Triangle Park, NC, 27707, USA., Alnajjar S; Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7AL, UK., Schaefer AM; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599, USA., Richardson Z; Inhalon Biopharma, Research Triangle Park, NC, 27707, USA., Wolf W; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599, USA., Stewart I; RTI International, Research Triangle Park, NC, 27709, USA., Sriboonyapirat P; Oregon State University, Corvallis, Oregon, 97331, USA., McCallen J; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599, USA., Farmer E; Inhalon Biopharma, Research Triangle Park, NC, 27707, USA., Nzati B; Inhalon Biopharma, Research Triangle Park, NC, 27707, USA., Lord S; Inhalon Biopharma, Research Triangle Park, NC, 27707, USA., Farrer B; Inhalon Biopharma, Research Triangle Park, NC, 27707, USA., Moench TR; Inhalon Biopharma, Research Triangle Park, NC, 27707, USA., Kumar PA; Department of Anesthesiology, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.; Outcomes Research Consortium, Cleveland, OH, 44195, USA., Arora H; Department of Anesthesiology, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Pickles RJ; Department of Microbiology & Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Hickey AJ; RTI International, Research Triangle Park, NC, 27709, USA., Ackermann M; USDA/ARS-National Animal Disease Center, Ames, IA, 50010, USA., Lai SK; Inhalon Biopharma, Research Triangle Park, NC, 27707, USA.; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599, USA.; Department of Microbiology & Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Mar; Vol. 11 (12), pp. e2306729. Date of Electronic Publication: 2024 Jan 15.
DOI: 10.1002/advs.202306729
Abstrakt: 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.
(© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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