Feasibility Studies of Nebulized SARS-CoV-2 Neutralizing Antibody in Mice and Cynomolgus Monkeys.
Pharm Res
; 39(9): 2191-2201, 2022 Sep.
Article
en En
| MEDLINE
| ID: mdl-35882740
ABSTRACT
PURPOSE:
Neutralizing antibodies, administrated through intravenous infusion, have shown to be highly efficacious in treating mild and moderate COVID-19 caused by SARS-CoV-2 infection in the lung. However, antibodies do not transport across the plasma-lung barrier efficiently, and up to 100 mg/kg dose was used in human causing significant supply and cost burdens. This study was to explore the feasibility of nebulized antibodies inhalation delivery as an alternative route.METHODS:
HB27, a potent RBD-specific humanized monoclonal antibody (Zhu et al. in National Sci Rev. 8nwaa297, 2020), showed excellent protection against SARS-CoV-2 in animal model and good safety profile in clinical studies. The pharmacokinetics and preliminary safety of HB27 administrated through the respiratory tract were studied in mice and cynomolgus monkeys here.RESULTS:
At a single 5 mg/kg dose, the peak HB27 concentration in mice pulmonary epithelial lining fluid (ELF) reached 857.8 µg/mL, 670-fold higher than the PRNT90 value of 1.28 µg/mL, and maintained above PRNT90 over 240 h. In contrast, when administrated by intravenous injection at a 5 mg/kg dose, the antibody concentrations in mice ELF were below PRNT90 value throughout, and were about 50-fold lower than that in the serum. In cynomolgus monkeys administrated with a single dose through inhalation, the antibody concentration in ELF remained high within 3 days. No drug-related safety concerns were observed in the studies.CONCLUSIONS:
The study demonstrated that nebulized neutralizing antibody delivery though inhalation could be a more efficient and efficacious alternative approach for treating COVID-19 and other respiratory infectious diseases, and warrants further evaluation in clinical studies.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
SARS-CoV-2
/
Tratamiento Farmacológico de COVID-19
Idioma:
En
Revista:
Pharm Res
Año:
2022
Tipo del documento:
Article