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

Abstract

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) TCID(50) by peroral or intramuscular (i.m.) administration. Furthermore, six mice received 10(5.8) TCID(50) intracerebrally (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) TCID(50)) in foxes, six of eight animals developed rabies virus-neutralizing antibodies (VNA). All foxes immunized by direct injection (10(7.7) TCID(50)) in the membrane of the jejunum were shown to seroconvert. Pre-existing immunity against canine adenovirus did not hinder the development of rabies VNA after oral application of the construct (10(8.0) TCID(50)). Fox cubs (24-29 days old) born from rabies-immune vixens were shown to develop very high levels of rabies VNA after i.m. administration (10(8.0) TCID(50)), indicating that the immunogenicity of the construct could surpass maternally transferred immunity. In dogs, the construct (10(8.0) TCID(50)) induced a very strong immune response after i.m. administration. However, no immune response was detectable in dogs after direct oral administration (10(8.3) TCID(50)) or after endoscopic deposition in the smaller intestine (10(8.0) TCID(50)). Hence, it must be concluded that the construct is not suitable for oral vaccination of dogs against rabies.