Recombinant Stabilized Prefusion Protein of Respiratory Syncytial Virus for Use as a Subunit Vaccine

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.

Potential Commercial Applications:		Competitive Advantages:
Vaccine for Respiratory Syncytial Virus		Vaccine stably exposes antigenic site in RSV F that permits generation of potent RSV neutralizing antibodies. There is currently no RSV vaccine on the market.

Development Stage:

• Pre-clinical
In vivo data available (animal)

Inventors:

Michael Joyce (NIAID)  ➽ more inventions...

Jason McLellan (NIAID)  ➽ more inventions...

Barney Graham (NIAID)  ➽ more inventions...

Peter Kwong (NIAID)  ➽ more inventions...

Baoshan Zhang (NIAID)  ➽ more inventions...

Masaru Kanekiyo (NIAID)  ➽ more inventions...

Man Chen (NIAID)  ➽ more inventions...

Jeffrey Boyington (NIAID)  ➽ more inventions...

Gwo-Yu Chuang (NIAID)  ➽ more inventions...

Ivelin Georgiev (NIAID)  ➽ more inventions...

Jason Gorman (NIAID)  ➽ more inventions...

Gilad Ofek (NIAID)  ➽ more inventions...

Marie Pancera (NIAID)  ➽ more inventions...

Mallika Sastry (NIAID)  ➽ more inventions...

Yongping Yang (NIAID)  ➽ more inventions...

Sanjay Srivatsan (NIAID)  ➽ more inventions...

Tongqing Zhou (NIAID)  ➽ more inventions...

Lei Chen (NIAID)  ➽ more inventions...

Cinque Soto (NIAID)  ➽ more inventions...

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


Intellectual Property:
US Pat: 9,738,689 issued 2017-08-22
US Pat: 10,017,543 issued 2018-07-10
US Application No. 61/780,910 filed on 2013-03-13
US Application No. 61/798,389 filed on 2013-03-15
US Application No. 61/857,613 filed on 2013-07-23
US Application No. 61/863,909 filed on 2013-08-09
PCT Application No. PCT/US2014/026714 filed on 2014-03-13
US Application No. 15/633,578 filed on 2017-06-26
US Application No. 16/025,858 filed on 2018-07-02

Publications:
McLellan JS, et al. PMID 23618766
McLellan JS, et al. PMID 24179220

Licensing Contact:
Carol Salata, Ph.D.
Email: csalata@mail.nih.gov
Phone: 240-627-3727

OTT Reference No: E-081-2013-0
Updated: Jun 22, 2018