Diminished Effectiveness of Neutralizing Antibodies for Respiratory Illnesses Due to Mass Transfer Limitations

Respiratory illnesses, such as whopping cough, RSV, and influenza, present a two-faced challenge for the design of bio-therapeutics. Immune recognition is easily overcome by common techniques such as library screening, phage display, and single-cell phenotyping. Yet, effectively neutralizing antibodies are often ineffective in vivo. We identify this discontinuity as a result of a mass transfer limitation. The common routes of antibody introduction to the body lack the lung localization that is seen in respiratory illnesses. We show here that an anti-Bordetella pertussis antibody is over 90% effective at neutralizing immune cell invasion in vitro, but exhibits nominal protection in an in vivo murine model when injected intraperitoneally. Rather, when directly administered to the lungs by a nanoparticle-assisted aerosol route, the in vitro predicted protection is observed. While further work is investigating a more practical route for larger proteins, we propose here an essential consideration in respiratory antibody engineering design.