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-na ïve and RSV experienced populations.The invention relates...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research