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, and also is an important cause of morbidity and mortality in the elderly. A licensed vaccine or antiviral drug suitable for routine use remains unavailable. This invention relates to the use of murine pneumonia virus (MPV—previously known as pneumonia virus of mice, PVM—of family Pneumovirida e) as a vaccine vector expressing the RSV fusion protein F, the most important protective antigen of RSV. MPV is not a human pathogen and is not restricted by immunity to common human viruses. MPV replicates in the superficial epithelial cells of the respiratory mucosa and is expected to be attenuated in humans based on the strong host range restriction observed in non-human primates. To generate these MPV/RSV vector vaccine candidates, the RSV F ORF was codon optimized, 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 similarly high levels of RSV-neutralizing serum antibodies that reached peak titers by fourteen (14) days post-vaccination. Thus, 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. RSV F was expressed in the wild-type form, but can readily be engineered to be stabilized in the highly immunogenic prefusion form, as has been done with parainfluenza virus vectors.

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.