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 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.
Potential Commercial Applications:
• Viral diagnostics
• Vaccine research
Competitive Advantages:
• Ease of manufacture
• Multivalent live attenuated vaccines
• B cell and T cell activation
• Low-cost vaccines
Development Stage:
In vivo data assessment (animal)
Inventors: Shirin Munir (NIAID), Linda Brock (NIAID), Ursula Buchholz (NIAID), Peter Collins (NIAID).
Intellectual Property: HHS Reference No. E-018-2018/0—U.S. Provisional Application No. 62/661,320, filed April 23, 2018 (pending).
Licensing And Collaborative Research 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., 301-594-8730; peter.soukas@nih.gov.