Prefusion Coronavirus Spike Proteins and Their Use


Coronaviruses (CoVs) can cause severe respiratory disease with high fatality rates in humans. The 2002-2003 SARS-CoV epidemic resulted in 8098 cases and 744 deaths, and MERS-CoV, which emerged in 2012, has resulted in 2144 cases and over 750 deaths as of March 2018. Currently, there are no effective prophylactic or therapeutic measures, and because other CoVs are poised to emerge as new human pathogens, there is a need to define a general CoV vaccine solution. Past efforts to develop CoV vaccines have used whole-inactivated virus, live-attenuated virus, recombinant protein subunit, or genetic approaches.

CoV spike (S) proteins mediate cellular attachment and membrane fusion and are therefore the target of protective antibodies. Inventors at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases have developed a novel CoV S protein vaccine antigen. This technology employs protein engineering to stabilize S in its prefusion conformation, preventing structural rearrangement, and exposing antigenically preferable surfaces. The technology has been applied to several CoV spikes, including those from human-relevant viruses, such as HKU1-CoV, SARS-CoV, and MERS-CoV. Particularly for MERS-COV, stabilized S proteins have been shown to elicit superior neutralizing antibody responses up to 10-fold higher in animal models and protect mice against lethal MERS-CoV infection. This technology is applicable for delivery via other platforms, such as mRNA.

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:
  • The stabilized prefusion coronavirus spike protein can be used as a vaccine antigen to elicit robust neutralizing antibody responses.
 
  • Improved immunogenicity compared to other coronavirus S vaccine formulations.
  • Increased protein expression, stability, and manufacturability compared to wild-type CoV S.


Inventors:

Barney Graham (NIAID)  ➽ more inventions...


Intellectual Property:
PCT Application No. PCT/US2017/058370
US Application No. 62/412,703
US Application No. 16/344,774

Collaboration Opportunity:

The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize norovirus diagnostics or vaccines. For collaboration opportunities, please contact Amy Petrik, Ph.D., 240-627-3721; amy.petrik@nih.gov.


Licensing Contact:
Amy Petrik, Ph.D., J.D.
Email: amy.petrik@nih.gov
Phone: 240-627-3721

OTT Reference No: E-234-2016-0
Updated: Oct 12, 2018