Substitutions-Modified Prefusion RSV F Proteins and Their Use

The respiratory syncytial virus (RSV) fusion (F) glycoprotein is the primary target of neutralizing antibodies. The F glycoprotein exists in at least two conformations, a meta-stable prefusion state, and an extremely stable postfusion state. Both states share several epitopes targeted by neutralizing antibodies, but it has been demonstrated that the prefusion conformation of F contains at least one epitope not present in the postfusion conformation. Natural infection results in neutralizing antibodies that are primarily directed against the prefusion conformation of F, not its postfusion conformation. The instability of the prefusion form of F has hindered both its characterization and its use as a vaccine antigen.

Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases have overcome technical obstacles to produce a homogeneous, soluble RSV F glycoprotein vaccine which is stabilized in the prefusion conformation and has improved stability and immunogenicity compared to the native protein. Additionally, several modifications were introduced to remove the requirement for furin during production, resulting in an increase in expression levels of the immunogen. Stability of the immunogen was increased 20-fold as compared to DS-CAV1 (a prefusion-stabilized RSV F glycoprotein vaccine candidate that is currently being assessed in clinical trials) upon incubation at 60 ºC. In mice, these immunogens elicited neutralization titers that were 2 to 5-fold higher than DS-CAV1.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404, as well as for further development and evaluation under a research collaboration.