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.

Potential Commercial Applications: Competitive Advantages:
  • Vaccine: RSV vaccine for human use.
  • Probe: B cell-sorting probe to isolate potent neutralizing monoclonal antibodies.
  • Diagnostics: To assess the titer of prefusion-specific antibodies in sera.
 
  • Increased stability compared to the current leading RSV vaccine candidate (DS-Cav1).
  • Elicits increased neutralization titers in mice.


Related Invention(s):
E-081-2013-0


Inventors:

Barney Graham (NIAID)  ➽ more inventions...

Peter Kwong (NIAID)  ➽ more inventions...

Yaroslav Tsybovsky (NIAID)  ➽ more inventions...

Michael Joyce (NIAID)  ➽ more inventions...

Baoshan Zhang (NIAID)  ➽ more inventions...

Man Chen (NIAID)  ➽ more inventions...

John Mascola (NIAID)  ➽ more inventions...

Aliaksandr Druz (NIAID)  ➽ more inventions...

Wing-pui Kong (NIAID)  ➽ more inventions...

Ivelin Georgiev (NIAID)  ➽ more inventions...

Paul Thomas (NIAID)  ➽ more inventions...

Marie Pancera (NIAID)  ➽ more inventions...

Mallika Sastry (NIAID)  ➽ more inventions...

Cinque Soto (NIAID)  ➽ more inventions...

Guillaume Stewart-Jones (NIAID)  ➽ more inventions...

Yongping Yang (NIAID)  ➽ more inventions...

Emily Rundlet (NIAID)  ➽ more inventions...

Li Ou (NIAID)  ➽ more inventions...

Ulrich Baxa (NIAID)  ➽ more inventions...

Joseph Van Galen (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 62/314,946
PCT Application No. PCT/US2017/024714
US Application No. 16/089,993

Publications:
Joyce MG, et al. PMID: 27478931

Licensing Contact:
Vince Contreras, Ph.D.
Email: vincent.contreras@nih.gov
Phone: 240-669-2823

OTT Reference No: E-064-2016-0
Updated: Oct 17, 2018