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

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  • Additional Information
    • Source:
      Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Weinheim : WILEY-VCH, [2014]-
    • Subject Terms:
      Antibodies, Monoclonal*/therapeutic use ; Respiratory Syncytial Virus Infections*/drug therapy; Humans ; Infant ; Child ; Animals ; Sheep ; Mice ; Aged ; Palivizumab/therapeutic use ; Respiratory Syncytial Viruses ; Lung
    • Abstract:
      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.)
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    • Grant Information:
      R43AI155185 United States NH NIH HHS; R43 AI149894 United States AI NIAID NIH HHS; R44 AI141054 United States AI NIAID NIH HHS; UL1 TR002489 United States TR NCATS NIH HHS; R43AI149894 United States NH NIH HHS; R44AI141054 United States NH NIH HHS; R44AI138728 United States NH NIH HHS; R43 AI155185 United States AI NIAID NIH HHS; R01 AI165853 United States AI NIAID NIH HHS; R44 AI138728 United States AI NIAID NIH HHS; R01AI165853 United States NH NIH HHS
    • Contributed Indexing:
      Keywords: RSV; mAb nebulization; monoclonal antibody; nebulization; respiratory syncytial virus
    • Accession Number:
      0 (Antibodies, Monoclonal)
      DQ448MW7KS (Palivizumab)
    • Publication Date:
      Date Created: 20240116 Date Completed: 20240328 Latest Revision: 20240330
    • Publication Date:
      20240330
    • Accession Number:
      PMC10966576
    • Accession Number:
      10.1002/advs.202306729
    • Accession Number:
      38225749