Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation

Seow, Han Cong; Cai, Jian‐Piao; Pan, Harry W.; Luo, Cheng; Wen, Kai; Situ, Jianwen; Wang, Kun; Cao, Hehe; Leung, Susan W.S.; Yuan, Shuofeng; Lam, Jenny K.W.

doi:10.1016/j.jconrel.2023.04.029

Cited by 7 publications

(1 citation statement)

References 41 publications

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“…At a single 5 mg/kg nebulized dose, the peak HB27 concentration in mice’s pulmonary epithelial lining fluid reached 857.8 μg/mL, 670-fold higher than the PRNT 90 value of 1.28 μg/mL, and was maintained above PRNT 90 over 240 h. 35 Dual administration of WKS13 mAb in particles below 5 mm (by 2-fluid nozzle) or above 10 mm (by ultrasonic nozzle) to the lung and nasal cavity of hamsters, respectively, was effective in offering prophylactic protection against the SARS-CoV-2 Delta variant. 36 …”

Section: Resultsmentioning

confidence: 99%

Respiratory delivery of passive immunotherapies for SARS-CoV-2 prophylaxis and therapy

Focosi,

Maggi

2023

Human Vaccines & Immunotherapeutics

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Convalescent plasma has been extensively tested during the COVID-19 pandemic as a transfusion product. Similarly, monoclonal antibodies have been largely administered either intravenously or intramuscularly. Nevertheless, when used against a respiratory pathogen, respiratory delivery is preferable to maximize the amount of antibody that reaches the entry door in order to prevent sustained viral multiplication. In this narrative review, we review the different types of inhalation device and summarize evidence from animal models and early clinical trials supporting the respiratory delivery (for either prophylactic or therapeutic purposes) of convalescent plasma or monoclonal antibodies (either full antibodies, single-chain variable fragments, or camelid-derived monoclonal heavy-chain only antibodies). Preliminary evidences from animal models suggest similar safety and noninferior efficacy, but efficacy evaluation from clinical trials is still limited.

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Section: Resultsmentioning

confidence: 99%

Respiratory delivery of passive immunotherapies for SARS-CoV-2 prophylaxis and therapy

Focosi,

Maggi

2023

Human Vaccines & Immunotherapeutics

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Dry powder formulations of hyperimmune serum

Bianchera,

Donofrio,

Sonvico

et al. 2024

Drug Deliv. and Transl. Res.

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Effective strategies against the spread of respiratory viruses are needed, as tragically demonstrated during the COVID-19 pandemic. Apart from vaccines, other preventive or protective measures are necessary: one promising strategy involves the nasal delivery of preventive or protective agents, targeting the site of initial infection. Harnessing the immune system’s ability to produce specific antibodies, a hyperimmune serum, collected from an individual vaccinated against SARS-CoV-2, was formulated as a dry powder for nasal administration. The selection of adequate excipients and process are key to maintaining protein stability and modulating the aerodynamic properties of the powders for reaching the desired respiratory regions. To this end, a hyperimmune serum was formulated with trehalose and mannitol as bulking agents during spray drying, then the ability of the redissolved immunoglobulins to bind Spike protein was verified by ELISA; foetal bovine serum was formulated in the same conditions as a reference. Moreover, a seroneutralization assay against SARS-CoV-2 pseudoviruses generated from different variants of concern was performed. The neutralizing ability of the serum was slightly reduced with respect to the starting serum when trehalose was used as a bulking agent. The powders were loaded in hypromellose capsules and aerosolized employing a nasal insufflator in an in vitro model of the nasal cavity connected to a Next Generation Impactor. The analysis of the powder distribution confirmed that all powders were inhalable and could target, at the same time, the upper and the lower airways. This is a preliminary proof-of-concept that this approach can constitute an effective strategy to provide broad coverage and protection against SARS-CoV-2, and in general against viruses affecting the airway. According to blood availability from donors, pools of hyperimmune sera could be rapidly formulated and administered, providing a simultaneous and timely neutralization of emerging viral variants. Graphical Abstract

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