Collins, Peter (NIAID)
Buchholz, Ursula (NIAID)
Brock, Linda (NIAID)
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.
- Viral diagnostics
- Vaccine research
- Ease of manufacture
- Multivalent live attenuated vaccines
- B cell and T cell activation
- Low-cost vaccines