Immunogenicity of an E1-deleted recombinant human adenovirus against rabies by different routes of administration

The immunogenic properties of an E1-deleted, human adenovirus type 5 (Ad5) vaccine virus with activity against rabies were examined in mice, foxes and dogs using different routes of administration. NMRI mice received 10(5.8), 10(5.3), 10(4.3), 10(3.3) and 10(2.3) TCID50 by peroral or intramuscular ( i.m.) administration. Furthermore, six mice received 10(5.8) TCID50 intrace rebrally (i.c.). The construct elicited marked seroconversion in mice after oral administration. Immunoreactivity in mice was even more pronounced i.m . and i.c. After direct oral administration (10(8.0) TCID50) in foxes, six of eight animals developed rabies virus-neutralizing antibodies (VNA). All foxes immunized by direct injection (10(7.7) TCID50) in the membrane of the jejunum were shown to seroconvert. Pre-existing immunity against canine ad enovirus did not hinder the development of rabies VNA after oral applicatio n of the construct (10(8.0) TCID50). Fox cubs (24-29 days old) born from ra bies-immune vixens were shown to develop very high levels of rabies VNA aft er i.m. administration (10(8.0) TCID50), indicating that the immunogenicity of the construct could surpass maternally transferred immunity. In dogs, t he construct (10(8.0) TCID50) induced a very strong immune response after i .m. administration. However, no immune response was detectable in dogs afte r direct oral administration (10(8.3) TCID50) or after endoscopic depositio n in the smaller intestine (10(8.0) TCID50). Hence, it must be concluded th at the construct is not suitable for oral vaccination of dogs against rabie s.