EFFICACY OF ADENOVIRUS-VECTORED RESPIRATORY SYNCYTIAL VIRUS-VACCINES IN A NEW FERRET MODEL

In the absence of an adequate small animal model for testing the effic acy of adenovirus-vectored respiratory syncytial virus (RSV) vaccines, a ferret model was established for this purpose. Recombinant adenovir us types 4, 5 and 7 expressing the RSV fusion glycoprotein (F), the at tachment glycoprotein (G) or both F and G were constructed previously. These recombinants contain a deletion of a large portion of the E3 re gion of the respective adenovirus vector. In addition, an Ad7(E3+)F re combinant virus which contains an intact E3 region was constructed to assess whether E3 region functions might enhance vaccine immunogenicit y. Evaluation of these viruses in the ferret model demonstrated that A d4 and Ad5 recombinants, administered intranasally to ferrets, induce stronger seroresponses to RSV than do Ad7 recombinant viruses. Ad7(E3)F did not show enhanced immunogenicity relative to E3-deleted recombi nant viruses. However, measurement of RSV infectivity in nasal washes, following intranasal RSV challenge, showed that five different vaccin ation regimens, Ad7F/Ad4F, Ad7G/Ad4G, Ad7FG/Ad4FG, Ac14F/Ad7(E3+)F and AdSF/Ad4F, protected ferrets from Rsv infection in a dose-dependent m anner.