Recombinant canine distemper virus vaccine against canine distemper and leishmaniasis

#1. Field of the Invention

#The present invention relates to a recombinant canine distemper virus which is useful as a vaccine against canine distemper and leishmaniasis, a vaccine comprising the recombinant virus, and an antiserum obtained from an animal inoculated with the vaccine. 2. Description of the Prior Art

#Canine distemper occurs naturally in animals such as the families Canidae and Mustelidae. It is characterized by symptoms such as fever, respiratory disorders such as pneumonia and bronchitis, diarrhea and nervous disorders. This disease is one of the representative infectious diseases in canines. It has been controlled for about thirty years by inoculation with live vaccines, but recently it has been reported that the occurrence of this disease is increasing worldwide, including in Japan. Even vaccinated dogs sometimes develop the disease, indicating that there is a possibility that the prior art vaccination cannot completely control the currently widespread field isolates. It has been reported that when examining the cross neutralizing reaction of the serum obtained from infected dogs against the vaccine strain, the reactivity against the vaccine strain was low. Recently isolated field isolates have mutations in the H gene encoding membrane protein, which is important for infection. Dogs are used as an experimental animal for physiological or pharmaceutical studies, as a disease model for humans, and for studies of infectious diseases, and they are recognized to be useful to industry. Also, dogs have played an important role in the social life of humans as domestic animals for thousands of years. Therefore, the protection of dogs from canine distemper is desired eagerly in many fields.

#FIG. 1 is a scheme for construction of pCDV(5+)-LACK.

#FIG. 2 is a growth curve of CDV-LACK in B95a cells.

#FIG. 3 shows the change in body weight of test animals after vaccination with CDV-LACK.

#The recombinant canine distemper virus of the present invention is characterized in that a gene encoding a protein concerned with protection against leishmaniasis infection is inserted into the viral genome.

#The recombinant canine distemper virus of the present invention may be prepared by using the method for reconstituting canine distemper virus described in Japanese Patent Application Kokai (Laid-Open) No. 2001-275684. For example, the recombinant cDNA comprising cDNA of the canine distemper virus genome having a desired foreign gene incorporated therein may be constructed. Then, this recombinant cDNA may be introduced into a cell expressing genes relating to transcription and replication along with a unit capable of intracellularly transcribing RNA from the cDNA as a temperate to reconstitute canine distemper virus particles.

#Canine distemper virus for use in preparing the recombinant canine distemper virus may be a canine distemper virus capable of inducing a high level of neutralizing antibodies against field canine distemper virus. Examples of the canine distemper viruses include strain Yanaka and strain Hamamatsu. Vaccine strains such as strain Onderstepoort may be used as long as this strain is modified by genetic engineering so as to induce the corresponding neutralizing antibodies.