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

Impfstoffwerk Dessau-Tornau GmbH, PO Box 214, 06855 Rosslau, Germany¹
Institute for Epidemiological Diagnostics, Federal Research Centre for Virus Diseases of Animals, Seestrasse 55, 16868 Wusterhausen, Germany²
Micromun GmbH, Walther-Rathenau Strasse 49a, 17489 Greifswald, Germany³
Microbix Biosystems Inc., 341 Bering Avenue, Toronto, Ontario, CanadaM8Z 3A8⁴

Author for correspondence: Ad Vos. Fax +49 34901 885797. e-mail ad.vos{at}idt-direct.de

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 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 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 adenovirus did not hinder the development of rabies VNA after oral application of the construct (10^8·0 TCID₅₀). 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 TCID₅₀), indicating that the immunogenicity of the construct could surpass maternally transferred immunity. In dogs, the construct (10^8·0 TCID₅₀) 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 TCID₅₀) or after endoscopic deposition in the smaller intestine (10^8·0 TCID₅₀). Hence, it must be concluded that the construct is not suitable for oral vaccination of dogs against rabies.

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