Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates

by Paule Hermet, Benoît Delache, Cecile Herate, Esther Wolf, Gaily Kivi, Erkki Juronen, Karl Mumm, Eva Žusinaite, Denis Kainov, Eve Sankovski, Kai Virumäe, Anu Planken, Andres Merits, Jessica E. Besaw, Ai Woon Yee, Takefumi Morizumi, Kyumhyuk Kim, Anling Kuo, Asma Berriche, Nathalie Dereuddre-Bosquet, Quentin Sconosciuti, Thibaut Naninck, Francis Relouzat, Mariangela Cavarelli, Mart Ustav, Derek Wilson, Oliver P. Ernst, Andres Männik, Roger LeGrand, Mart Ustav Jr.

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.