Recombinant Replication-defective Adenovirus Based Rabies Vaccine Research

Rabies is a kind of deadly zoonosis caused by rabies virus, a virus possesses an unsegmented negative-strand RNA genome. Vaccination is the only effective way to prevent and control this disease.Although various regular rabies vaccines have shown their efficiency in controlling the incidence of rabies,they are too expensive and too fragile to be used for widelives, such as dogs, foxes and raccoons,who are reserviors of the virus. The control and eradication of rabies demands the development of novel effective and economical rabies vaccines. Adenovirus and vaccinia based recombinant rabies vaccine are good candidates for such a purpose. Compared to recombinant vaccinia, recombinant adenovirus is safer and more effective, and it can also be used for vaccination of newborn shortly after birth, when maternally transferred immune effectors are high and still protective.Previous study demonstrated that rabies virion is composed of a single molecule of genomic RNA and five proteins showing post-translational modification. Although all the viral proteins may be antigenicity, the glycoprotein is the only rabies antigen that consistently induces virus-neutralizing antibodies, and the nucleoprotein could also enhance the T-helper cell immune response to rabies vaccination. To develop novel adenovirus-based recombinant rabies vaccine, the brain tissue of a rabid mouse was used to isolate viral RNA, the cDNA of glycoprotein gene was obtained by RT-PCR, followed by amplification of DNA fragment with high fidelity PCR system. The coding sequence of the glycoprotein gene was cloned into pUC18 plasmid and then sequenced. The sequence was accepted by Genbank with an accession number of AF325714. MegAlign analysis indicated that this glycoprotein gene was derived from rabies CVS-N2c,which is a variant of CVS24 strain with high neuropathogenicity. The gene is 1575 bp, coding for 524 amino acids. When compared to the glycoprotein gene of fixed...