Mononegavirales Vectors expressing Chimeric Antigens


Human respiratory syncytial virus (RSV) continues to be the leading viral cause of severe acute lower respiratory tract disease in infants and children worldwide. A licensed vaccine or antiviral drug suitable for routine use remains unavailable. This invention relates to the use of murine pneumonia virus (MPV), a virus to which humans normally are not exposed to and that is not cross-protected with RSV, as a vector to express the RSV fusion (F) glycoprotein as an RSV vaccine candidate. The RSV F ORF was codon optimized. The RSV F ORF was placed under the control of MPV transcription signals and inserted at the first (rMPV-F1), third (rMPV29 F3), or fourth (rMPV-F4) gene position of a version of the MPV genome that contained a codon pair optimized L polymerase gene. The recovered viruses replicated in vitro as efficiently as the empty vector, with stable expression of RSV F protein. Replication and immunogenicity of rMPV-F1 and rMPV-F3 were evaluated in rhesus macaques following administration by the combined intranasal and intratracheal routes. Both viruses replicated at low levels in the upper and lower respiratory tract, maintained stable RSV F expression, and induced similar high levels of RSV-neutralizing serum antibodies that reached peak titers by fourteen (14) days post-vaccination. rMPV provides a highly attenuated yet immunogenic vector for the expression of RSV F protein, with potential application in RSV-naïve and RSV experienced populations.

The invention relates to live, chimeric non-human Mononegavirales vectors that allow a cell to express at least one protein from at least one human pathogen as well as compositions comprising the vectors, methods and kits for eliciting an immune response in a host, and methods of making the vectors.

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:
  • Viral diagnostics
  • Vaccine research
 
  • Ease of manufacture
  • Multivalent live attenuated vaccines
  • B cell and T cell activation
  • Low-cost vaccines


Inventors:

Shirin Munir (NIAID)  ➽ more inventions...

Linda Brock (NIAID)  ➽ more inventions...

Ursula Buchholz (NIAID)  ➽ more inventions...

Peter Collins (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 62/661,320
PCT Application No. PCT/US2019/028771

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 for development of a vaccine for respiratory or other infections. For collaboration opportunities, please contact Peter Soukas, J.D., at Peter.Soukas@nih.gov or 301-594-8730.


Licensing Contact:
Peter Soukas, J.D.
Email: peter.soukas@nih.gov
Phone: 301-496-2644

OTT Reference No: E-018-2018-0
Updated: May 7, 2018