부산대학교 도서관

The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses. Author summary: COVID-19, caused by the SARS-CoV-2 virus, has had a global impact since the beginning of 2020. Although vaccines were developed and accepted under emergency procedures in under a year–certain populations still remain vulnerable for the viral infection. Monoclonal antibodies could be very potent against viral infections and respiratory diseases, but SARS-CoV-2 has presented many challenges in that field. One being the speed of emerging mutations, which has prevented many developed antibodies from working against later variants, and the other is the route of administration. Here, we developed two monoclonal antibodies of which one lost its virus neutralizing activity due to the mutations in Spike protein. As the second antibody maintained its effectiveness despite the mutational dynamics, we tested it in a viral challenge with non-human primates. We show that nebulization of therapeutic antibody provides significantly higher antibody concentrations in the lungs and airways, where most of the viral replication takes place. Therefore, nebulization could provide a more accessible and effective way of managing respiratory viruses, minimizing potential side effects and cost. [ABSTRACT FROM AUTHOR]