A monoclonal anti-SARS-COV-2 IgG administered by intravenous or nebulization route reduces viral load in upper and lower respiratory tract

A monoclonal anti-SARS-COV-2 IgG administered by intravenous or nebulization route reduces viral load in upper and lower respiratory tract

Benoît Delache¹^*, Cécile Hérate^1*, Paule Hermet², Andres Männik², Quentin Sconosciuti¹, Francis Relouzat¹, Asma Berriche¹ , Thibaut Nanninck¹, Nathalie Deureuddre-Bosquet¹, Roger Le Grand¹ and Mart Ustav Jr²,

^aUniversité Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.

^bIcosagen Cell Factory OÜ, Tartu, Estonia,

Summary

Icosagen developed an anti-Sars-COV-2 neutralising monoclonal antibody (VH16VL104) effective in vitro against multiple variants of the virus including the Delta and Omicron variants of concern (VOC). We developed an optimized prototype for respiratory tract delivery customized for Non-Human Primate (NHP) in spontaneous breathing by adapting a vibrating mesh nebulizer (VMN) from Aerogen (Aeroneb solo) to a facemask fitted with unidirectional valves. The effectiveness of the device has been confirmed by positron emission tomography coupled to X-ray scan (PET-CT) imaging after 18-FDG nebulization on three macaques. The therapeutic efficacy of the nebulized (Neb) VH16VL104 was assessed in cynomolgus macaques 24 hours after exposure to a high dose (10⁵ TCID50/animal by intranasal & tracheal route) of Sars-COV2. We compared the nebulization route with intravenous (IV) bolus administration. The antibody treatment was administrated as a single dose of 25mg.kg^-1. Nebulization administration results in antibody concentrations in broncho alveolar lavages (BAL) more than 10 times higher than the IV route 48 hours post-treatment and a systemic passage resulting in serum concentrations 100 times lower than the IV route. The antibody is present in the blood of all animals for at least 28 days after administration. The VH16VL104 treatment efficacy on viral load measured in nasopharyngeal swabs and BALs was statistically significant regardless of the route of treatment administration. Our data suggest that mesh vibrating nebulization is of interest for patients requiring immediate strong antiviral effect in the lung. This route of administration, in complement to IV, could be used against other pathogens when a therapeutic pulmonary bolus is crucial.

Key Message

We showed in a macaque preclinical model of COVID19 that a neutralising monoclonal IgG developed by Icosagen is efficient against SARS-COV-2 and reduced viral load when administered 24 hours after exposure to the virus. Aerosol antibody therapy with a VMN provides immediate higher lung concentrations (BAL) compared to IV and systemic persistence.