Inhalable Nanobody (PiN-21) prevents and treats SARS-CoV-2 infections in Syrian hamsters at ultra-low doses

• Published in: Science advances 2021-05, Vol.7 (22)
• Main Authors: Nambulli, Sham, Xiang, Yufei, Tilston-Lunel, Natasha L, Rennick, Linda J, Sang, Zhe, Klimstra, William B, Reed, Douglas S, Crossland, Nicholas A, Shi, Yi, Duprex, W Paul
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosols - administration & dosage; Animals; Coronavirus; COVID-19 - prevention & control; COVID-19 Drug Treatment; Disease Models, Animal; Female; Male; Mesocricetus; Pandemics - prevention & control; Pneumonia, Viral - drug therapy; Pneumonia, Viral - prevention & control; SARS-CoV-2 - drug effects; SciAdv r-articles; Single-Domain Antibodies - administration & dosage; Viral Load - drug effects
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abh0319

Globally, there is an urgency to develop effective, low-cost therapeutic interventions for coronavirus disease 2019 (COVID-19). We previously generated the stable and ultrapotent homotrimeric Pittsburgh inhalable Nanobody 21 (PiN-21). Using Syrian hamsters that model moderate to severe COVID-19 disease, we demonstrate the high efficacy of PiN-21 to prevent and treat SARS-CoV-2 infection. Intranasal delivery of PiN-21 at 0.6 mg/kg protects infected animals from weight loss and substantially reduces viral burdens in both lower and upper airways compared to control. Aerosol delivery of PiN-21 facilitates deposition throughout the respiratory tract and dose minimization to 0.2 mg/kg. Inhalation treatment quickly reverses animals' weight loss after infection, decreases lung viral titers by 6 logs leading to drastically mitigated lung pathology, and prevents viral pneumonia. Combined with the marked stability and low production cost, this innovative therapy may provide a convenient and cost-effective option to mitigate the ongoing pandemic.