The invention, a stabilized recombinant prefusion F protein (pre F), is a candidate subunit vaccine for Respiratory Syncytial Virus (RSV). Pre-F is stabilized in the prefusion conformation and displays epitopes not present in postfusion F protein. Several potent RSV neutralizing antibodies bind pre F, but not postfusion F. Therefore, immunization with pre F may elicit an immune response superior to the response generated by postfusion F.

NIH researchers have engineered pre F to expose an antigenic site 0, which is targeted by extremely potent RSV neutralizing antibodies. Structure-based design yielded several stabilized variants of pre F that maintained exposure of antigenic site 0 when subjected to extremes of pH, osmolality and temperature.

Preclinical in vivo data on stabilized pre F is available. Immunization of mice and macaques with antigenic site 0 stabilized pre F variants elicited high levels of RSV specific neutralizing activity.