Therapeutic delivery of ALX‐0171 Nanobody reduces disease severity of human respiratory syncytial virus strain M37 after established RSV infection

Abstract

Respiratory syncytial virus (RSV) is the most common reason for hospitalization of infants with viral pneumonia but lacks a therapy that is fully satisfactory and effective. ALX‐0171 is a Nanobody directed against RSV F protein that reduces RSV infection and disease severity. In order to determine the optimal dose of therapeutic delivery of ALX‐0171 after RSV infection, three doses of ALX‐0171 (0, 1.4, 2.8 and 11 mg) were delivered by nebulization to lambs at 3, 4, and 5 days after infection with a human strain of RSV (Memphis 37 strain) and assessed for efficacy at 2, 4 and 6 days post infection. Lambs not receiving ALX‐0171 had limited or lacked RSV gross and microscopic lesions, RSV viral antigen in lung and RSV titers at 2 days post RSV but these lesions and viral parameters increased progressively at days 4 and 6. There was a dose‐effect relationship yielding in vivo IC50 and lambs treated with ALX‐0171 lacked lesions 2 days post RSV infection and had reduced lesions and viral parameters at 4 and 6 days post RSV infection compared to lesions in lambs not receiving treatment. These studies determined that ALX‐0171 reduces RSV disease severity when administered after RSV inoculation. Clinically, infants commonly do not receive treatment for RSV until after clinical signs develop and work in this study suggests that ALX‐0171 has potential to reduce RSV disease severity in the face of established RSV infection at optimized doses.Support or Funding InformationThese studies were funded by Ablynx NVThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.